Bibliography, page 9

1. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 10963686
   Diversity and phylogeny of gephyrin: tissue-specific splice variants, gene structure, and sequence similarities to molybdenum cofactor-synthesizing and cytoskeleton-associated proteins.

   Ramming M, Kins S, Werner N, Hermann A, Betz H, Kirsch J · Proc Natl Acad Sci U S A 2000
   used by GPHN (gephyrin) — synaptic scaffold and molybdenum-cofactor enzyme, KMT2A fusion partner in t(11;14)(q23;q24)
2. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 10914540
   Late effects in survivors of infant leukemia

   Leung W, Hudson M, Zhu Y, Rivera GK, Ribeiro RC, Sandlund JT, Bowman LC, Evans WE, Kun L, Pui CH · Leukemia 2000
   used by Growth and endocrine consequences of being treated for leukemia as a baby, What the treated brain looks like later: neurocognitive late effects after CNS-directed therapy in infancy
3. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 11114197
   Activation of the myocyte enhancer factor-2 transcription factor by calcium/calmodulin-dependent protein kinase-stimulated binding of 14-3-3 to histone deacetylase 5.

   McKinsey TA, Zhang CL, Olson EN · Proc Natl Acad Sci U S A 2000
   used by HDAC5 - the eraser in an existing entry's own id, and the one HDAC in this graph that erases a mark on a fusion partner protein rather than on a histone
4. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 11069025
   The amino terminus targets the mixed lineage leukemia (MLL) protein to the nucleolus, nuclear matrix and mitotic chromosomal scaffolds

   Caslini C, Alarcon AS, Hess JL, Tanaka R, Murti KG, Biondi A · Leukemia 2000
   used by Hypothesis: KMT2A's AT-hooks are a DNA-topology reader, not an AT-sequence reader — which would link the fusion's address to the scaffold-attachment architecture that also makes its own gene fragile, Hypothesis: where a KMT2A fusion sits in the nucleus is set entirely by retained KMT2A modules, and no partner changes the compartment - so every published 'the fusion is here' result is a wild-type KMT2A result, KMT2A / MLL1 — the gene that breaks, MLL was reported at regions attached to the nuclear envelope in 2000, which is indirect evidence at the lamina that this graph currently records as absent, Nuclear matrix and mitotic chromosome scaffold — KMT2A sits with topoisomerase II, in the same place the gene breaks, The KMT2A::MLLT3 chimeric protein: what survives the join on each side, in residue numbers - and the four AF9 modules that do not, The nuclear lamina and lamina-associated domains - evidence grade for KMT2A: weak and indirect, not none, The nucleolus — the one compartment with direct published images of a KMT2A fusion inside it, The three AT-hooks (aa 169-180, 217-227, 301-309) as a localisation determinant — and the correction that MLL's hooks read DNA *structure*, not AT-richness, Three CXXC-pathway activities converge on rDNA - KDM2B represses Pol I, KMT2A and SETD1A bind the whole locus, MLL-AF4 is predominantly nucleolar - and no paper contains two of them, Where KMT2A::MLLT3 sits in the nucleus: two papers, both overexpression, both from before 2005 - and the fusion carries no AF9 import signal
5. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 10915021
   Enhanced sensitivity to alkylating agent in lymphocytes from patients with multiple endocrine neoplasia type 1.

   Itakura Y, Sakurai A, Katai M, Ikeo Y, Hashizume K · Biomed Pharmacother 2000
   used by Menin-FANCD2: one 2003 co-immunoprecipitation, a curated sufficient region of menin 214-390, and nothing since
6. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 10893414
   Characterization of the histone H1-binding protein, NASP, as a cell cycle-regulated somatic protein.

   Richardson RT, Batova IN, Widgren EE, Zheng LX, Whitfield M, Marzluff WF, O'Rand MG · J Biol Chem 2000
   used by NASP - the soluble histone reservoir, and the only gene in this beat with a real selective difference at a pan-essentiality shallow enough to interpret
7. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 10931000
   Generation of the NUP98-HOXD13 fusion transcript by a rare translocation, t(2;11)(q31;p15), in a case of infant leukaemia

   Shimada H, et al. · British Journal of Haematology 110(1):210-213 2000
   used by NUP98::HOXD13, t(2;11)(q31;p15) — the myelodysplasia fusion, and a warning against targeting p53
8. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 10623634
   NXP-1, a human protein related to Rad21/Scc1/Mcd1, is a component of the nuclear matrix.

   Sadano H, Sugimoto H, Sakai F, Nomura N, Osumi T · Biochem Biophys Res Commun 2000
   used by RAD21 - the cohesin subunit with the most break-prone sites in KMT2A-rearranged patients, and the degron experiment this graph keeps asking for
9. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 10882070
   Crystal structure of a heterodimeric complex of RAR and RXR ligand-binding domains

   Bourguet W, Vivat V, Wurtz JM, Chambon P, Gronemeyer H, Moras D · Molecular Cell 2000
   used by RARA — domain architecture and residue coordinates
10. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 10716941
    The MAR-binding protein SATB1 orchestrates temporal and spatial expression of multiple genes during T-cell development

    Alvarez JD, Yasui DH, Niida H, Joh T, Loh DY, Kohwi-Shigematsu T · Genes Dev 2000
    used by SATB1 - a nuclear-matrix and PML-body genome organiser with its own matrix-targeting sequence, the clearest subnuclear-localization entry in this beat, and a T-lineage factor that B cells do not need
11. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 10652260
    Association of mammalian SMC1 and SMC3 proteins with meiotic chromosomes and synaptonemal complexes.

    Eijpe M, Heyting C, Gross B, Jessberger R · J Cell Sci 2000
    used by SMC3 - the cohesin ATPase arm, the only subunit whose partial loss has been tested directly against a KMT2A fusion, and it was tolerated
12. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 11076961
    Characterization of vertebrate cohesin complexes and their regulation in prophase.

    Sumara I, Vorlaufer E, Gieffers C, Peters BH, Peters JM · J Cell Biol 2000
    used by STAG2 - the cohesin subunit that defines secondary AML, and the one whose loss a KMT2A fusion does not care about
13. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 10861294
    DNA structural properties of AF9 are similar to MLL and could act as recombination hot spots resulting in MLL/AF9 translocations and leukemogenesis

    Strissel PL, Strick R, Tomek RJ, Roe BA, Rowley JD, Zeleznik-Le NJ · Human Molecular Genetics 2000
    used by The KMT2A breakpoint cluster region: an 8.3 kb stretch built to break, Topoisomerase II cleavage and TOP2 poisons as a source of KMT2A breaks
14. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 10688900
    The amino terminus of the mixed lineage leukemia protein (MLL) promotes cell cycle arrest and monocytic differentiation

    Caslini C, Shilatifard A, Yang L, Hess JL · Proceedings of the National Academy of Sciences USA 2000
    used by The three AT-hooks (aa 169-180, 217-227, 301-309) as a localisation determinant — and the correction that MLL's hooks read DNA *structure*, not AT-richness
15. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 11066077
    Cytogenetic and molecular analysis of the acute monocytic leukemia cell line THP-1 with an MLL-AF9 translocation.

    Odero MD, Zeleznik-Le NJ, Chinwalla V, et al. · Genes Chromosomes Cancer 2000
    used by THP-1 (CVCL_0006): the default KMT2A::MLLT3 line, from a one-year-old, carrying NRAS G12D and a TP53 frameshift
16. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 10887138
    Altered lymphoid development in mice deficient for the mAF4 proto-oncogene.

    Isnard P, Coré N, Naquet P, Djabali M · Blood 2000
    used by Three of the four AFF scaffolds have a named human Mendelian syndrome and the index fusion's partner has none — a 0/4 that is a fact about AFF1 and not about how hard anyone has looked
17. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 10615047
    DNA topoisomerase IIbeta and neural development.

    Yang X, Li W, Prescott ED, Burden SJ, Wang JC · Science 2000
    used by TOP2B - the isoform most etoposide-induced KMT2A breaks depend on, resolved genetically and not resolvable pharmacologically
18. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 11025664
    The function of PML in p53-dependent apoptosis.

    Guo A, Salomoni P, Luo J, Shih A, Zhong S, Gu W, Pandolfi PP · Nat Cell Biol 2000
    used by TP53 - named in 84 entries of this graph, absent from the index genome study of the disease, and four different things depending on when you look
19. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 10860745
    Biochemical analyses of the AF10 protein: the extended LAP/PHD-finger mediates oligomerisation.

    Linder B, Newman R, Jones LK, Debernardi S, Young BD, Freemont P, Verrijzer CP, Saha V · J Mol Biol 2000
    used by Wild-type AF10 is called nuclear on a construct and found in both fractions in tissue - and that disagreement decides whether CALM-AF10's cytoplasmic life is a gain or an inheritance
20. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 10490026
    Acinus is a caspase-3-activated protein required for apoptotic chromatin condensation

    Sahara S, Aoto M, Eguchi Y, et al. · Nature 1999
    used by ACIN1 (Acinus) - a splicing/apoptosis protein whose only domain is the 35-residue module the leukaemic fusion keeps, and whose entire localization record is uncoded
21. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 10416593
    Rapid isolation of chromosomal breakpoints from patients with t(4;11) acute lymphoblastic leukemia: implications for basic and clinical research

    Reichel M, Gillert E, Breitenlohner I, Repp R, Greil J, Beck JD, Fey GH, Marschalek R · Cancer Research 1999
    used by Alu repeats and nuclear-matrix anchors in the KMT2A breakpoint region — the genome-feature side of the break
22. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 10467413
    A DNA damage repair mechanism is involved in the origin of chromosomal translocations t(4;11) in primary leukemic cells

    Gillert E, Leis T, Repp R, et al. · Oncogene 1999
    used by Analysis (runnable): mine the KMT2A junction sequences for repair-pathway signature, and count the one junction class with a genetic control behind it, Programmed DNA breaks - V(D)J and class switching - and the verdict on whether either one breaks KMT2A, RAG off-target activity: the dominant mutator in ETV6::RUNX1 ALL, and probably not the cause of KMT2A fusions, Which repair pathway glues the fusion together: classical NHEJ vs alternative end joining
23. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 10530057
    Clinical and biological aspects of acute lymphoblastic leukemia in 62 infants: retrospective analysis of the Tokyo Children's Cancer Study Group.

    Isoyama K, Okawa H, Hayashi Y, Hanada R, Okimoto Y, Maeda M, et al. · Pediatr Int 1999
    used by Big liver, big spleen: the organomegaly numbers measured in infants, not pooled from children, CNS disease at diagnosis in infants: a real excess, measured by a procedure that partly creates it, The white cell count at diagnosis in infants, and why the reported medians disagree by fivefold, WBC 300, age 6 months, MRD 0.01%: three lines drawn by committees, not by biology
24. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 10525530
    PML is critical for ND10 formation and recruits the PML-interacting protein daxx to this nuclear structure when modified by SUMO-1.

    Ishov AM, Sotnikov AG, Negorev D, Vladimirova OV, Neff N, Kamitani T, Yeh ET, Strauss JF, Maul GG · J Cell Biol 1999
    used by DAXX - the strongest of five selective dependencies among 254 unwritten interactors but it FAILS Bonferroni correction (p=0.0128, rank 4 of 254), and not one paper connects it to this disease
25. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 10421373
    The chromatin-specific transcription elongation factor FACT comprises human SPT16 and SSRP1 proteins

    Orphanides G, Wu WH, Lane WS, Hampsey M, Reinberg D · Nature 400(6741):284-8 1999
    used by FACT (SPT16-SSRP1) - the chromatin arm of transcription elongation, and a clean negative result for the KMT2A::AFF1 interactome, SSRP1 - the small FACT subunit, and the only protein in this beat that binds a confirmed KMT2A-fusion interactor directly (LEDGF/p75, via HMG box to PWWP), SUPT16H (SPT16) - the large FACT subunit: pan-essential, an anti-dependency in KMT2A-rearranged lines, and drugged in MLL-r leukaemia by a compound that works through p53
26. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 10373536
    Fanconi anemia proteins FANCA, FANCC, and FANCG/XRCC9 interact in a functional nuclear complex.

    Garcia-Higuera I, Kuang Y, Näf D, Wasik J, D'Andrea AD · Mol Cell Biol 1999
    used by FANCG — FA core complex; rank 27 of 8,269 for KMT2A-selective dependency, and no KMT2A literature at all
27. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 10531433
    Loss of postsynaptic GABA(A) receptor clustering in gephyrin-deficient mice.

    Kneussel M, Brandstätter JH, Laube B, Stahl S, Müller U, Betz H · J Neurosci 1999
    used by GPHN (gephyrin) — synaptic scaffold and molybdenum-cofactor enzyme, KMT2A fusion partner in t(11;14)(q23;q24)
28. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 10444591
    Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation.

    Zhang Y, Ng HH, Erdjument-Bromage H, Tempst P, Bird A, Reinberg D · Genes & Development 1999
    used by HDAC1 and HDAC2 belong to at least five different corepressor complexes, so an HDAC1/2 observation names no complex - and this graph carried both enzymes without the scaffolds that would tell them apart, MBD3 (O95983) - the methyl-CpG-binding subunit that does NOT bind methylated DNA, and a validated KMT2A::AFF1-selective CRISPR vulnerability that is absent from every column of the pan-fusion interactome, MTA2 / MTA1L1 (O94776) - the NuRD scaffold that clamps HDAC1, recruited in T lymphocytes by BCL11B, and absent together with MTA1 and MTA3 from every column of the pan-MLL-fusion interactome, SIN3A (Q96ST3) - the scaffold of the OTHER HDAC1/2 corepressor complex, a 5' fusion partner in infant B-ALL and in myelodysplasia, and present in three MLL-fusion AP-MS columns but not the index fusion's, The MLL-fusion interactome recovers corepressor SCAFFOLDS and not their HDAC1/2 catalytic core: NuRD splits 5/7 remodelling arm versus 0/7 deacetylase arm (Fisher p = 0.021), and HDAC1, HDAC2, RBBP4 and RBBP7 are absent from all seven baits, The NuRD complex - two separable modules, three paralogue choices that change what it does, and a graph that carried its ATPase and its shared core but never the scaffolds that make it NuRD
29. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 9989505
    Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription

    Agarwal SK, Guru SC, Heppner C, Erdos MR, Collins RM, Park SY, Saggar S, Chandrasekharappa SC, Collins FS, Spiegel AM, Marx SJ, Burns AL · Cell 96:143-52 1999
    used by How menin silences JunD: pocket binding plus uncoupling from MAP kinase signalling, JUND - the AP-1 subunit menin holds down, and the one a menin inhibitor lets go, JUND liberation — the drug's mechanism of action and one of its mechanisms of resistance are the same event, Menin-JunD: the same pocket, the same drug, the opposite job, Releasing JunD does not merely de-repress it: JunD without menin becomes a growth promoter
30. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 10369681
    Aiolos transcription factor controls cell death in T cells by regulating Bcl-2 expression and its cellular localization.

    Romero F, Martinez-A C, Camonis J, et al. · EMBO Journal 1999
    used by IKZF3 / Aiolos (Q9UKT9) - the B-lymphoid transcription factor that goes UP under both inhibitors, regulates BCL2, and is a degradable drug target
31. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 10383129
    Recurrent involvement of 2p23 in inflammatory myofibroblastic tumors

    Griffin CA, Hawkins AL, Dvorak C, Henkle C, Ellingham T, Perlman EJ · Cancer Research 1999
    used by Is KMT2A::AFF1 leukemia epithelial or endothelial? No — it is haematopoietic. But the question is a good one
32. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 10602411
    Standardized RT-PCR analysis of fusion gene transcripts from chromosome aberrations in acute leukemia for detection of minimal residual disease. Report of the BIOMED-1 Concerted Action: investigation of minimal residual disease in acute leukemia.

    van Dongen JJ, Macintyre EA, Gabert JA, et al. · Leukemia 1999
    used by Junction RT-PCR is the one routine assay in this disease that IS fusion-specific - and it is structurally blind to KMT2A*, MRD by fusion transcript: fast, standardised, partner-limited - and structurally blind to KMT2A*, Step 5: molecular confirmation and naming the partner
33. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 10473643
    A role for the GSG domain in localizing Sam68 to novel nuclear structures in cancer cell lines.

    Chen T, Boisvert FM, Bazett-Jones DP, Richard S · Mol Biol Cell 1999
    used by KHDRBS1 (Sam68) — an RNA-binding protein that holds the MLL-AF4 message DOWN, a class no dropout screen can find
34. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 10229319
    Enhanced myeloid specificity of CD117 compared with CD13 and CD33.

    Nomdedeu JF, ..., Rubiol E · Leuk Res 1999
    used by KIT / CD117 - the most myeloid-specific antigen in the lineage-assignment panel, and the mutation that is mutually exclusive with KMT2A rearrangement
35. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.reviewPMID 10481267
    Epidermal growth factor pathway substrate 15, Eps15.

    Salcini AE, Chen H, Iannolo G, De Camilli P, Di Fiore PP · Int J Biochem Cell Biol 1999
    used by KMT2A::EPS15 (MLL-AF1p), t(1;11)(p32;q23) — the infant-ALL cytoplasmic partner
36. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 10458233
    Childhood acute lymphoblastic leukemia with the MLL-ENL fusion and t(11;19)(q23;p13.3) translocation

    Rubnitz JE, Camitta BM, Mahmoud H, et al. · Journal of Clinical Oncology 1999
    used by KMT2A::MLLT1 (MLL-ENL), t(11;19)(q23;p13.3)
37. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 10025907
    MLL-AF1q fusion resulting from t(1;11) in acute leukemia.

    Busson-Le Coniat M, Salomon-Nguyen F, Hillion J, Bernard OA, Berger R · Leukemia 1999
    used by KMT2A::MLLT11 (MLL-AF1q), t(1;11)(q21;q23) — 28 patients, and not one functional experiment
38. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 10339604
    MSF (MLL septin-like fusion), a fusion partner gene of MLL, in a therapy-related acute myeloid leukemia with a t(11;17)(q23;q25).

    Osaka M, Rowley JD, Zeleznik-Le NJ · Proc Natl Acad Sci U S A 1999
    used by KMT2A::SEPTIN9 (MLL-SEPT9 / MLL-MSF), t(11;17)(q23;q25), SEPTIN9 (septin-9 / MSF) — cytoskeletal GTPase, KMT2A fusion partner in t(11;17)(q23;q25)
39. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 10485469
    AF17q25, a putative septin family gene, fuses the MLL gene in acute myeloid leukemia with t(11;17)(q23;q25).

    Taki T, Ohnishi H, Shinohara K, et al. · Cancer Res 1999
    used by KMT2A::SEPTIN9 (MLL-SEPT9 / MLL-MSF), t(11;17)(q23;q25), SEPTIN9 (septin-9 / MSF) — cytoskeletal GTPase, KMT2A fusion partner in t(11;17)(q23;q25)
40. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 10201409
    Autoinhibition by an internal nuclear localization signal revealed by the crystal structure of mammalian importin alpha.

    Kobe B · Nat Struct Biol 1999
    used by KPNA2 / importin-alpha-1 (P52292) - the classical NLS receptor in the pan-MLL-fusion core, and the ONLY karyopherin of any kind in the whole 960-protein network
41. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 10551495
    Prenatal origin of acute lymphoblastic leukaemia in children

    Wiemels JL, Cazzaniga G, Daniotti M, et al. · Lancet 1999
    used by Mechanism class 2 — transcription-factor corruption (RUNX1::RUNX1T1, PML::RARA, ETV6::RUNX1, CBFB::MYH11) — a balance, not a pure dominant negative, Ordering the fusions developmentally — which stage of blood formation each one hijacks, and at what age the child presents
42. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 10612394
    The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder.

    Stewart GS, et al. · Cell 1999
    used by MRE11 (P49959, 708 aa) - the nuclease that makes the first cut of end resection, named in 10 entries of this graph and never written; DepMap mean -0.542 with 56% of 1,258 lines below -0.5, the deepest dependency in the whole resection cascade
43. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 9858599
    CREB binding protein interacts with nucleoporin-specific FG repeats that activate transcription and mediate NUP98-HOXA9 oncogenicity

    Kasper LH, et al. · Molecular and Cellular Biology 19(1):764-776 1999
    used by NUP98::HOXA9, t(7;11)(p15;p15) — the founding NUP98 fusion, and an incomplete oncogene
44. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 10556215
    The t(11;20)(p15;q11) chromosomal translocation associated with therapy-related myelodysplastic syndrome results in an NUP98-TOP1 fusion

    Ahuja HG, et al. · Blood 94(9):3258-3261 1999
    used by NUP98::TOP1, t(11;20)(p15;q11~q12) — the most precisely mapped NUP98 breakpoint, and the reciprocal that was wrong twice
45. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 10215622
    The subcellular localization of PBX1 and EXD proteins depends on nuclear import and export signals and is modulated by association with PREP1 and HTH

    Berthelsen J, Kilstrup-Nielsen C, Blasi F, Mavilio F, Zappavigna V · Genes & Development 13:946-953 1999
    used by PBX proteins are not constitutively nuclear: a MEINOX partner keeps them there by blocking export - and nobody has ever looked at PBX3 in a KMT2A-rearranged cell, PBX3 - the TALE cofactor the field says is non-redundant, and the experiment that says HOXA9 is the redundant one, The druggable node in the homeodomain code is the MEIS1-PBX3 interface, not the HOX-PBX one - and it is the only one nobody has attacked
46. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 10052460
    Structure of a HoxB1-Pbx1 heterodimer bound to DNA: role of the hexapeptide and a fourth homeodomain helix in complex formation

    Piper DE, Batchelor AH, Chang CP, Cleary ML, Wolberger C · Cell 1999
    used by PBX1 — domain architecture and residue coordinates
47. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 10082572
    HOXA9 forms triple complexes with PBX2 and MEIS1 in myeloid cells.

    · Mol Cell Biol 1999
    used by PBX2 - an AFF4 co-purifying protein in two rounds of one AP-MS atlas, and the PBX paralogue the leukaemia literature explicitly excluded
48. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 10436022
    Clathrin assembly lymphoid myeloid leukemia (CALM) protein: localization in endocytic-coated pits, interactions with clathrin, and the impact of overexpression on clathrin-mediated traffic.

    Tebar F, et al. · Mol Biol Cell 1999
    used by PICALM (CALM) - the clathrin-assembly adaptor that is the 5' partner of CALM::AF10, Where wild-type PICALM actually is: coated pits, the Golgi, coated vesicles - and a nuclear pool nobody has explained
49. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 10490642
    Leukemic HRX fusion proteins inhibit GADD34-induced apoptosis and associate with the GADD34 and hSNF5/INI1 proteins.

    Adler HT, Chinery R, Wu DY, Kussick SJ, et al. · Molecular and Cellular Biology 19(10):7050-60 1999
    used by PPP1R15A / GADD34 (O75807) - the eIF2alpha phosphatase adaptor, and KMT2A fusion proteins were shown to BIND it and block its apoptosis in 1999, a paper this graph has never cited
50. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 10597311
    SIAH-1 inhibits cell growth by altering the mitotic process.

    Bruzzoni-Giovanelli H, Faille A, Linares-Cruz G, Nemani M et al. · Oncogene 1999
    used by SIAH1 — the E3 ligase that degrades AFF1, and that the reciprocal AF4::KMT2A fusion escapes
51. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 10574707
    Cell cycle regulation of PML modification and ND10 composition.

    Everett RD, Lomonte P, Sternsdorf T, van Driel R et al. · J Cell Sci 1999
    used by SUMO1 - not a complex partner of LEDGF but a modifier of it, and the interactome row cannot tell you which
52. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 10518215
    SLUG, a ces-1-related zinc finger transcription factor gene with antiapoptotic activity, is a downstream target of the E2A-HLF oncoprotein

    Inukai T, Inoue A, Kurosawa H, Goi K, Shinjyo T, Ozawa K, Mao M, Inaba T, Look AT · Mol Cell 1999
    used by TCF3::HLF (E2A-HLF), t(17;19)(q22;p13)
53. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    PDB entry 1B72: PBX1, homeobox protein HOX-B1/DNA ternary complex

    RCSB Protein Data Bank · RCSB PDB 1999
    used by TCF3::PBX1 (E2A-PBX1), t(1;19)(q23;p13.3)
54. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 9694699
    ABI-1, a human homolog to mouse Abl-interactor 1, fuses the MLL gene in acute myeloid leukemia with t(10;11)(p11.2;q23).

    Taki T, Shibuya N, Taniwaki M, et al. · Blood 1998
    used by ABI1 (Abl interactor 1 / e3B1) — WAVE-complex cytoskeletal adaptor, KMT2A partner, and an ENL-binding protein, KMT2A::ABI1 (MLL-ABI1), t(10;11)(p11.2;q23) — the partner that binds an elongation partner
55. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 9845365
    Rapid and phosphoinositol-dependent binding of the SWI/SNF-like BAF complex to chromatin after T lymphocyte receptor signaling.

    Zhao K, Wang W, Rando OJ, Xue Y, Swiderek K, Kuo A, Crabtree GR · Cell 1998
    used by ACTB / beta-actin (P60709) as a SUBJECT, not a loading control - the dirtiest negative control in the pan-MLL-fusion 42, and the one the paper's authors kept
56. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 9482895
    The partial tandem duplication of ALL1 (MLL) is consistently generated by Alu-mediated homologous recombination in acute myeloid leukemia

    Strout MP, Marcucci G, Bloomfield CD, Caligiuri MA · Proceedings of the National Academy of Sciences USA 1998
    used by Alu repeats and nuclear-matrix anchors in the KMT2A breakpoint region — the genome-feature side of the break
57. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 9808577
    AF4 encodes a ubiquitous protein that in both native and MLL-AF4 fusion types localizes to subnuclear compartments.

    Li Q, Frestedt JL, Kersey JH · Blood 1998
    used by Anti-AFF1 antibodies: attributable on a gel, not attributable in a microscope, and the classic localisation result shows exactly why, Attribution audit 1 of 5 - who co-purifies with KMT2A::AFF1: the inventory does not survive, the individual partner blots mostly do, Attribution audit 3 of 5 - where KMT2A::AFF1 sits in the nucleus: the endogenous image does not survive, the overexpression images do and say something different, Attribution audit 4 of 5 - the half-life and turnover of KMT2A::AFF1: this class SURVIVES, and it is the only endogenous fusion-attributable protein measurement this beat found, Experiment: endogenously tagged KMT2A::AFF1 imaged through a menin-inhibitor time course, with a five-compartment segmentation and a half-life arm, Experiment: five-fraction subcellular blot of a t(4;11) line, with a menin-inhibitor arm - converting thirty years of unattributable images into attributable numbers using only existing antibodies, Hypothesis: menin inhibition does not merely displace KMT2A::AFF1 from chromatin, it destabilises it — the evicted fusion is degraded, not parked, Knock a tag-plus-degron cassette into the endogenous KMT2A::AFF1 allele in SEM - one construct that makes five claim classes attributable, Targeted PRM for the KMT2A::AFF1 junction peptide - the experiment that makes every other attribution claim testable, The endogenous MLL-AF4 localisation experiment was unattributable, not negative: an anti-AF4 polyclonal in a t(4;11) cell images mostly wild-type AF4, The five verdicts in one place, plus what this beat read and did not use, The MLL-side twin of the 1998 anti-AF4 result: in 1997 the same punctate nuclear pattern was seen with and without an 11q23 translocation, and the authors said so, The soluble-nucleoplasm versus chromatin-bound axis - the one localisation readout that keeps a size dimension, and nobody has run it on a KMT2A fusion, The working attribution reagent in this literature is not an antibody, it is the gel - and that single fact predicts which claim classes survive
58. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 9722603
    The human polycomb group complex associates with pericentromeric heterochromatin to form a novel nuclear domain.

    Saurin AJ; Shiels C; Williamson J; Satijn DP; Otte AP; Sheer D; Freemont PS · J Cell Biol 1998
    used by BMI1 - the self-renewal gene that KMT2A fusions can do without, because HOXA9 covers for it at the same locus
59. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 9482106
    Active cdk6 complexes are predominantly nuclear and represent only a minority of the cdk6 in T cells.

    Mahony D, Parry DA, Lees E · Oncogene 1998;16:603-11 1998
    used by CDK6 - the kinase the KMT2A-r rationale actually rests on, and the pan-essentiality flag and the selectivity are both true
60. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 9614144
    Nucleosome assembly activity and intracellular localization of human CAF-1 changes during the cell division cycle.

    Marheineke K, Krude T · J Biol Chem 1998
    used by CHAF1B (CAF-1 p60) - the one histone chaperone in this beat with a real leukaemia literature, and a mouse experiment that contradicts DepMap's verdict on its druggability
61. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 9804427
    Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex.

    Tong JK, Hassig CA, Schnitzler GR, Kingston RE, Schreiber SL · Nature 1998
    used by CHD4 (Q14839) - the NuRD ATPase, a pan-MLL-fusion co-purifier, and the gene whose disruption drives lineage switching in KMT2A::AFF1 relapse, The NuRD complex - two separable modules, three paralogue choices that change what it does, and a graph that carried its ATPase and its shared core but never the scaffolds that make it NuRD
62. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 9881974
    RelB is essential for the development of myeloid-related CD8alpha- dendritic cells but not of lymphoid-related CD8alpha+ dendritic cells.

    Wu L, D'Amico A, Winkel KD, Suter M, Lo D, Shortman K · Immunity 1998
    used by Conventional (myeloid-related) dendritic cell - the DC lineage RELB actually builds, and the thymic part of that phenotype is architecture rather than a cell-intrinsic requirement
63. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 9560216
    Localization of nascent RNA and CREB binding protein with the PML-containing nuclear body.

    LaMorte VJ; Dyck JA; Ochs RL; Evans RM · Proc Natl Acad Sci U S A 1998
    used by CREBBP (CBP) — binds the KMT2A transactivation domain, which no fusion keeps
64. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 9738986
    Fluorescence in situ hybridization analysis of 12;21 translocation in Japanese childhood acute lymphoblastic leukemia.

    Eguchi-Ishimae M, Eguchi M, Tanaka K, Hamamoto K, Ohki M, Ueda K, Kamada N · Jpn J Cancer Res 1998
    used by DUX4::IGH (IGH-DUX4), t(4;14)/ins(14;4) — D4Z4 repeat insertion into the IGH locus
65. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 9751059
    IKAP is a scaffold protein of the IkappaB kinase complex.

    Cohen L, Henzel WJ, et al. · Nature 1998
    used by ELP1 (IKBKAP/IKAP) - the Elongator scaffold that was first named for the IKK complex, is a paediatric-cancer predisposition gene, and has an RNA Pol II contact in IntAct
66. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 9721102
    Structure and Asn-Pro-Phe binding pocket of the Eps15 homology domain

    de Beer T, Carter RE, Lobel-Rice KE, Sorkin A, Overduin M · Science 1998
    used by EPS15 (AF1p): the EH domains may or may not be discarded, and either way nobody has shown it matters
67. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    PDB entry 1EH2 — Structure of the second Eps15 homology domain of human Eps15; primary citation: Structure and Asn-Pro-Phe binding pocket of the Eps15 homology domain

    RCSB Protein Data Bank · RCSB Protein Data Bank / Science 1998
    used by EPS15 / AF1p — domain architecture, and the one coordinate nobody has published
68. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 9462753
    A novel ETV6-NTRK3 gene fusion in congenital fibrosarcoma

    Knezevich SR, McFadden DE, Tao W, Lim JF, Sorensen PH · Nature Genetics 1998
    used by ETV6::NTRK3 (ETV6-TRKC), t(12;15)(p13;q25), Is KMT2A::AFF1 leukemia epithelial or endothelial? No — it is haematopoietic. But the question is a good one
69. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 9652733
    Lack of TEL/AML1 fusion in pediatric AML: further evidence for lineage specificity of TEL/AML1

    Loh ML, McLean TW, Buckley JD, Howells W, Gilliland DG, Smith FO · Leuk Res 1998
    used by ETV6::RUNX1 (TEL-AML1), t(12;21)(p13;q22)
70. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 9552022
    EWS-FLI1 fusion transcript structure is an independent determinant of prognosis in Ewing's sarcoma

    de Alava E, Kawai A, Healey JH, et al. · Journal of Clinical Oncology 1998
    used by EWSR1 — domain architecture and residue coordinates, FLI1 — domain architecture and residue coordinates
71. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 9418860
    The oncogenic capacity of HRX-ENL requires the transcriptional transactivation activity of ENL and the DNA binding motifs of HRX

    Slany RK, Lavau C, Cleary ML · Molecular and Cellular Biology 1998
    used by Experiment: a topology-controlled binding survey of the MLL AT-hook region, plus a triple AT-hook alanine mutant in an endogenously tagged fusion, Step 1 — How the fusion finds its genes: AT-hooks and the CXXC domain reading unmethylated CpG, The three AT-hooks (aa 169-180, 217-227, 301-309) as a localisation determinant — and the correction that MLL's hooks read DNA *structure*, not AT-richness
72. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 9736752
    gas7: A gene expressed preferentially in growth-arrested fibroblasts and terminally differentiated Purkinje neurons affects neurite formation.

    Ju YT, Chang AC, She BR, Tsaur ML, Hwang HM, Chao CC, et al. · Proc Natl Acad Sci U S A 1998
    used by GAS7 — growth-arrest-specific F-BAR protein, the second pillar of the forced-oligomerisation model
73. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 9488723
    DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139.

    Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM · J Biol Chem 1998
    used by H2AX - filed as a gene and not as a mark, and the reason that decision changes what the graph can say
74. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 9463336
    Characterization of mutations in patients with multiple endocrine neoplasia type 1

    Bassett JH, Forbes SA, Pannett AA, Lloyd SE, Christie PT, Wooding C, Harding B, Besser GM, Edwards CR, Monson JP, Sampson J, Wass JA, Wheeler MH, Thakker RV · Am J Hum Genet 62:232-44 1998
    used by How long does menin have to be gone? Two months in a mouse islet, a decade or more in a human carrier, The MEN1 age-penetrance curve: 7% by age 10, 52% by 20, 87% by 30, The reversibility question: months of partial occupancy against a syndrome built from decades of loss, Turn menin off for a defined window, then back on: the missing experiment that would bound reversibility
75. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 9742243
    AT-hook motifs identified in a wide variety of DNA-binding proteins

    Aravind L, Landsman D · Nucleic Acids Research 1998
    used by Hypothesis: KMT2A's AT-hooks are a DNA-topology reader, not an AT-sequence reader — which would link the fusion's address to the scaffold-attachment architecture that also makes its own gene fragile, The three AT-hooks (aa 169-180, 217-227, 301-309) as a localisation determinant — and the correction that MLL's hooks read DNA *structure*, not AT-richness
76. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 9600980
    t(11;22)(q23;q11.2) In acute myeloid leukemia of infant twins fuses MLL with hCDCrel, a cell division cycle gene in the genomic region of deletion in DiGeorge and velocardiofacial syndromes.

    Megonigal MD, Rappaport EF, Jones DH, et al. · Proc Natl Acad Sci U S A 1998
    used by KMT2A::SEPTIN5 (MLL-SEPT5 / MLL-hCDCrel-1), t(11;22)(q23;q11.2)
77. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 9465067
    Menin, the product of the MEN1 gene, is a nuclear protein.

    Guru SC, Goldsmith PK, Burns AL, Marx SJ, Spiegel AM, Collins FS, Chandrasekharappa SC · Proc Natl Acad Sci U S A 1998
    used by MEN1 / menin — the adaptor the fusion cannot work without, Menin's two nuclear localisation signals, 479-497 and 588-608: mapped in 1998, verified residue-for-residue today, annotated by UniProt nowhere - NLS-1 in no structure at all, NLS-2 resolved in one
78. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 9590180
    Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome.

    Varon R, et al. · Cell 1998
    used by NBN / nibrin (O60934, 754 aa) - the MRN subunit whose loss causes a leukaemia-predisposition syndrome and yet is almost dispensable in DepMap: mean -0.047 against MRE11's -0.542 in the same complex, the same call and the same release
79. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 9865693
    Structure of an IkappaBalpha/NF-kappaB complex.

    Jacobs MD, Harrison SC · Cell 1998
    used by NFKB1 (p105/p50) — the only menin-NF-kB subunit with a co-immunoprecipitation, and the arm the MLL leukaemia data points at
80. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 9503016
    The pufferfish SLP-1 gene, a new member of the SCL/TAL-1 family of transcription factors.

    Göttgens B, Gilbert JG, Barton LM, Aparicio S, Hawker K, Mistry S, Vaudin M, King A, Bentley D, Elgar G, Green AR · Genomics 1998
    used by NHLH1 / HEN1 / NSCL1 - a TAL1-family bHLH factor found by cross-hybridising with the T-ALL oncogene, whose knockout mouse is normal and whose only imaging call puts it in the GOLGI
81. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 9679133
    Nopp140 functions as a molecular link between the nucleolus and the coiled bodies.

    Isaac C, Yang Y, Meier UT · J Cell Biol 1998
    used by NOLC1 / Nopp140 (Q14978) - a nucleolar and Cajal-body phosphoprotein in the pan-MLL-fusion core, and the first physical bridge to this graph's nucleolar convergence
82. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 9766650
    NUP98-HOXD13 gene fusion in therapy-related acute myelogenous leukemia

    Raza-Egilmez SZ, et al. · Cancer Research 58(19):4269-4273 1998
    used by NUP98::HOXD13, t(2;11)(q31;p15) — the myelodysplasia fusion, and a warning against targeting p53
83. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 9616163
    MLL and CALM are fused to AF10 in morphologically distinct subsets of acute leukemia with translocation t(10;11): both rearrangements are associated with a poor prognosis.

    Dreyling MH, Schrader K, et al. · Blood 1998
    used by One karyotype band, two partner genes: why t(11;19) and t(10;11) can cancel a real partner effect
84. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 9518481
    Functional association of poly(ADP-ribose) polymerase with DNA polymerase alpha-primase complex: a link between DNA strand break detection and DNA replication.

    Dantzer F, Nasheuer HP, Vonesch JL, de Murcia G, Ménissier-de Murcia J · Nucleic Acids Res 1998
    used by PARP1 - the target whose inhibitors this disease was specifically shown to resist, and which three later papers combine anyway
85. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 9756909
    Identification of three major sentrinization sites in PML

    Kamitani T, Kito K, Nguyen HP, Wada H, Fukuda-Kamitani T, Yeh ET · Journal of Biological Chemistry 273:26675-82 1998
    used by PML K160 SUMOylation - the retained-portion PTM that became an approved therapy, and the benchmark every other retained site should be measured against
86. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 9683585
    Germ-line mutation analysis in patients with multiple endocrine neoplasia type 1 and related disorders.

    Giraud S, Zhang CX, Serova-Sinilnikova O, Wautot V, Salandre J, Buisson N, et al., Calender A · Am J Hum Genet 63:455-67 1998
    used by Primary hyperparathyroidism in MEN1: the first and commonest consequence of losing menin, The MEN1 age-penetrance curve: 7% by age 10, 52% by 20, 87% by 30
87. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 9822615
    Isolation of cDNAs encoding novel transcription coactivators p52 and p75 reveals an alternate regulatory mechanism of transcriptional activation.

    Ge H, Si Y, et al. · EMBO J 1998
    used by PSIP1 makes two proteins and only one of them has the IBD: a p52 result is not a p75 result, and the knockout mouse removes both
88. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.journal-articlePMID 9881706
    Fine structure of translocation breakpoints in leukemic blasts with chromosomal translocation t(4;11): the DNA damage-repair model of translocation

    · Genes, Chromosomes and Cancer 1998
    used by RAG off-target activity: the dominant mutator in ETV6::RUNX1 ALL, and probably not the cause of KMT2A fusions, The other half of the break: what is actually known about the AFF1 breakpoint region, and the negative-control gene nobody cites
89. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 9808573
    An in vivo topoisomerase II cleavage site and a DNase I hypersensitive site colocalize near exon 9 in the MLL breakpoint cluster region

    Strissel PL, Strick R, Rowley JD, Zeleznik-Le NJ · Blood 1998
    used by The KMT2A breakpoint cluster region: an 8.3 kb stretch built to break
90. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 9885572
    NURD, a novel complex with both ATP-dependent chromatin-remodeling and histone deacetylase activities.

    Xue Y, Wong J, Moreno GT, Young MK, Cote J, Wang W · Molecular Cell 1998
    used by The NuRD complex - two separable modules, three paralogue choices that change what it does, and a graph that carried its ATPase and its shared core but never the scaffolds that make it NuRD
91. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 9570750
    Ret finger protein is a normal component of PML nuclear bodies and interacts directly with PML.

    Cao T, Duprez E, Borden KL, Freemont PS, Etkin LD · J Cell Sci 1998
    used by TRIM27 - the E3 ligase inside PRC1.1 that USP7 spends its time undoing, and the worst UniProt localisation record this graph has audited
92. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 9727489
    DNA transposition by the RAG1 and RAG2 proteins: a possible source of oncogenic translocations

    Hiom K, Melek M, Gellert M · Cell 1998
    used by V(D)J recombination: the immune system deliberately cuts its own chromosomes, using a domesticated transposon
93. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 9630231
    Partial V(D)J recombination activity leads to Omenn syndrome

    Villa A, Santagata S, Bozzi F, Vezzoni P, Spanopoulou E, et al. · Cell 1998
    used by V(D)J recombination: the immune system deliberately cuts its own chromosomes, using a domesticated transposon
94. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 9737688
    High frequency of fusion transcripts of exon 11 and exon 4/5 in AF-4 gene is observed in cord blood, as well as leukemic cells from infant leukemia patients with t(4;11)(q21;q23)

    Yamamoto S, Zaitsu M, Ishii E, Yatsuki H, Mizutani S, Eguchi M, Ihara K, Okamura T, Hara T, Miyazaki S · Leukemia 12:1398-403 1998
    used by What fraction of fusion-positive newborns ever get leukaemia? For ETV6::RUNX1, very few. For KMT2A, nobody knows, and the biology says the answer may be most of them
95. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 9878787
    Expression pattern and cellular distribution of the murine homologue of AF10.

    Linder B, Jones LK, Chaplin T, Mohd-Sarip A, Heinlein UA, Young BD, Saha V · Biochim Biophys Acta 1998
    used by Wild-type AF10 is called nuclear on a construct and found in both fractions in tissue - and that disagreement decides whether CALM-AF10's cytoplasmic life is a gain or an inheritance
96. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 9853615
    Selection system for genes encoding nuclear-targeted proteins.

    · Nat Biotechnol 1998
    used by ZEB2 — an EMT transcription factor that turns out to be a leukemia dependency and a guardian of lineage fidelity
97. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 9349501
    Chimeric MLL products with a Ras binding cytoplasmic protein AF6 involved in t(6;11)(q27;q23) leukemia localize in the nucleus

    Joh T, Yamamoto K, Kagami Y, Kakuda H, Sato T, Yamamoto T, Takahashi T, Ueda R, Kaibuchi K, Seto M · Oncogene 1997
    used by AFDN (AF6): nothing is discarded from the fusion, yet this is the clearest subtraction in the set — the fusion steals wild-type AF6 out of the cytoplasm, Enumeration for the subnuclear beat: every compartment queried, every count, and the papers that looked on-topic and were not used, Hypothesis: where a KMT2A fusion sits in the nucleus is set entirely by retained KMT2A modules, and no partner changes the compartment - so every published 'the fusion is here' result is a wild-type KMT2A result, KMT2A / MLL1 — the gene that breaks, MLL was reported at regions attached to the nuclear envelope in 2000, which is indirect evidence at the lamina that this graph currently records as absent, Nuclear import of every KMT2A fusion is a property of retained KMT2A sequence, and the determinant was mapped in 1997 to a region containing the AT-hook motifs, The soluble-nucleoplasm versus chromatin-bound axis - the one localisation readout that keeps a size dimension, and nobody has run it on a KMT2A fusion
98. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 9444945
    A human acute lymphoblastic leukemia line with the T(4;11) translocation as a model of minimal residual disease in SCID mice

    Gobbi A, Di Berardino C, Scanziani E, et al. · Leukemia Research 1997
    used by ALL-PO (CVCL_1069) — an infant KMT2A::AFF1 line that is already in DepMap and has never been screened
99. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 8988051
    MLL self fusion mediated by Alu repeat homologous recombination and prognosis of AML-M4/M5 subtypes

    So CW, Ma ZG, Price CM, Dong S, Chen SJ, Gu LJ, So CK, Wiedemann LM, Chan LC · Cancer Research 1997
    used by Alu repeats and nuclear-matrix anchors in the KMT2A breakpoint region — the genome-feature side of the break
100. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 9391133
     Backtracking leukemia to birth: identification of clonotypic gene fusion sequences in neonatal blood spots

     Gale KB, Ford AM, Repp R, et al. · Proceedings of the National Academy of Sciences of the United States of America 1997
     used by Analysis (runnable): mine the KMT2A junction sequences for repair-pathway signature, and count the one junction class with a genetic control behind it, Hypothesis: the KMT2A break can be prevented rather than the fusion treated - stated so it can be killed, and it probably should be, Hypothesis: the second hit in infant KMT2A-rearranged leukaemia is a fetal developmental window, not a mutation, In-utero origin, proven: clonotypic KMT2A::AFF1 junctions found in the patient's own newborn blood spot, KMT2A::AFF1 (MLL-AF4), t(4;11)(q21;q23), Latency: months from the fusion forming in a fetus to leukaemia in an infant, against years or a decade for every other backtracked fusion, Ordering the fusions developmentally — which stage of blood formation each one hijacks, and at what age the child presents, The prevention window: the break happens in a fetus, and we know when it CLOSES but not when it opens
101. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 9207083
     Nuclear punctate distribution of ALL-1 is conferred by distinct elements at the N terminus of the protein.

     Yano T, Nakamura T, Blechman J, et al. · Proc Natl Acad Sci U S A 1997
     used by Attribution audit 3 of 5 - where KMT2A::AFF1 sits in the nucleus: the endogenous image does not survive, the overexpression images do and say something different, Hypothesis: where a KMT2A fusion sits in the nucleus is set entirely by retained KMT2A modules, and no partner changes the compartment - so every published 'the fusion is here' result is a wild-type KMT2A result, MLL was reported at regions attached to the nuclear envelope in 2000, which is indirect evidence at the lamina that this graph currently records as absent, Where KMT2A and its fusions sit inside the nucleus — SNL1/SNL2, nuclear speckles and the condensate question
102. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 9041173
     The localization of the HRX/ALL1 protein to specific nuclear subdomains is altered by fusion with its eps15 translocation partner.

     Rogaia D, Grignani F, Carbone R, et al. · Cancer research 1997
     used by Attribution audit 3 of 5 - where KMT2A::AFF1 sits in the nucleus: the endogenous image does not survive, the overexpression images do and say something different, Hypothesis: where a KMT2A fusion sits in the nucleus is set entirely by retained KMT2A modules, and no partner changes the compartment - so every published 'the fusion is here' result is a wild-type KMT2A result, The endogenous MLL-AF4 localisation experiment was unattributable, not negative: an anti-AF4 polyclonal in a t(4;11) cell images mostly wild-type AF4
103. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.reviewPMID 9474863
     Multiple endocrine neoplasia type 1 and 2: from morphology to molecular pathology 1997

     Komminoth P · Verhandlungen der Deutschen Gesellschaft fur Pathologie 1997
     used by Auditing the seven strikes before applying them: nine of ten decisions stand, four for different reasons than were given, and one clinical argument fails, Target safety triage v2: constraint with its uncertainty attached (run), The phase-2 go/no-go register: the numbers we agree to before we look
104. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 9361035
     Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung

     Debelenko LV, Brambilla E, Agarwal SK, et al. · Human Molecular Genetics 1997
     used by Auditing the seven strikes before applying them: nine of ten decisions stand, four for different reasons than were given, and one clinical argument fails
105. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 9230194
     Infant acute leukemias show the same biased distribution of ALL1 gene breaks as topoisomerase II related secondary acute leukemias

     Cimino G, Rapanotti MC, Biondi A, et al. · Cancer Research 1997
     used by Breakpoint anatomy, and an audit of the prognosis claim
106. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 9376686
     Independent regulation of Fuc-TIV and Fuc-TVII genes leading to modulation of cell surface antigen expression in developing myeloid cells.

     Clarke JL, Watkins WM · Glycobiology 1997
     used by CD15 (Lewis-x, SSEA-1, 3-fucosyl-N-acetyllactosamine) - a sugar, not a protein: the most-named antigen in this graph that no gene encodes, CD65 - a neutral glycolipid epitope (V3FucnLc8Cer), no gene, and the CD number that was split in two because its antibodies did not agree, CD65s (VIM-2, sialylated ceramide dodecasaccharide) - the myeloid antigen that, with CD15, makes NG2 a perfect predictor of KMT2A rearrangement, FUT4 - the myeloid alpha-1,3-fucosyltransferase, a hub gene of the KMT2A-rearranged expression module, and the gene HGNC once officially called CD15
107. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 9305600
     Two acute monocytic leukemia (AML-M5a) cell lines (MOLM-13 and MOLM-14) with interclonal phenotypic heterogeneity showing MLL-AF9 fusion resulting from an occult chromosome insertion, ins(11;9)(q23;p22p23).

     Matsuo Y, MacLeod RA, Uphoff CC, et al. · Leukemia 1997
     used by Every human t(9;11) cell line, with every accession fetched and read back: eleven lines, ten patients, and two of them are B-ALL, Hypothesis: the haem and iron dependency of KMT2A-rearranged lines is monocytic physiology, not fusion biology — and the panel cannot tell us either way, Monoblast — the immature monocyte that names FAB M5a, the dominant morphology of congenital KMT2A leukaemia, The monocytic confound is worse than recorded: two of the six rearranged lines are one patient, and the four-line control group contains a HOXA-driven fusion and two NPM1c/myelomonocytic lines
108. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 8972230
     Overexpression of HOXA10 in murine hematopoietic cells perturbs both myeloid and lymphoid differentiation and leads to acute myeloid leukemia.

     Thorsteinsdottir U, Sauvageau G, Hough MR, Dragowska W, Lansdorp PM, Lawrence HJ, Largman C, Humphries RK · Mol Cell Biol 1997
     used by HOXA10 - named in 27 entries as part of the HOXA output and never written; a posterior HOX paralogue that is regulated with HOXA9 and tested far less often
109. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 9058712
     Mice bearing a targeted interruption of the homeobox gene HOXA9 have defects in myeloid, erythroid, and lymphoid hematopoiesis.

     Lawrence HJ, Helgason CD, Sauvageau G, Fong S, Izon DJ, Humphries RK, Largman C · Blood 1997
     used by HOXA9 — required for survival of established MLL-rearranged leukemia, and dispensable for starting it
110. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 9039264
     Meiosis-specific DNA double-strand breaks are catalyzed by Spo11, a member of a widely conserved protein family

     Keeney S, Giroux CN, Kleckner N · Cell 1997
     used by Is fusion intended in biology sometimes? Yes, and the answer has a strategic edge, Meiotic recombination: hundreds of deliberate DNA breaks per cell, made by a topoisomerase relative, at sites chosen by a single zinc-finger protein
111. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 9172002
     Chromosome 1 rearrangements involving the genes TPR and NTRK1 produce structurally different thyroid-specific TRK oncogenes

     Greco A, Miranda C, Pagliardini S, Fusetti L, Bongarzone I, Pierotti MA · Genes, Chromosomes & Cancer 1997
     used by Is KMT2A::AFF1 leukemia epithelial or endothelial? No — it is haematopoietic. But the question is a good one
112. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 9129143
     T-cell oncogene rhombotin-2 interacts with retinoblastoma-binding protein 2

     Mao S, Neale GA, Goorha RM · Oncogene 14:1531-1539 1997
     used by LMO2 (rhombotin-2) - a bridging LIM-only protein, higher in pro-B and MLL-rearranged B-ALL, anti-selective in KMT2A-rearranged lines, and a physical partner of the KDM5A module that NUP98::KDM5A retains
113. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 9121481
     Role of the nucleophosmin (NPM) portion of the non-Hodgkin's lymphoma-associated NPM-anaplastic lymphoma kinase fusion protein in oncogenesis.

     Bischof D, Pulford K, Mason DY, Morris SW · Molecular and Cellular Biology 1997
     used by NPM1::ALK (NPM-ALK), t(2;5)(p23;q35)
114. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 9277049
     Subcellular localization of the MEN, MLL/MEN and truncated MLL proteins expressed in leukemic cells carrying the t(11;19)(q23;p13.1) translocation

     Kanda Y, et al. · International journal of hematology 1997
     used by Nuclear import of every KMT2A fusion is a property of retained KMT2A sequence, and the determinant was mapped in 1997 to a region containing the AT-hook motifs, The soluble-nucleoplasm versus chromatin-bound axis - the one localisation readout that keeps a size dimension, and nobody has run it on a KMT2A fusion
115. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 9288109
     Fusion of retinoic acid receptor alpha to NuMA, the nuclear mitotic apparatus protein, by a variant translocation in acute promyelocytic leukaemia.

     Wells RA, Catzavelos C, Kamel-Reid S · Nature Genetics 1997
     used by NUMA1 / NuMA (Q14980) - a nuclear-matrix protein that becomes the spindle pole, and the 5' partner of a variant APL fusion whose coiled-coil is required for oncogenicity
116. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 9166830
     The inv(11)(p15q22) chromosome translocation of de novo and therapy-related myeloid malignancies results in fusion of the nucleoporin gene, NUP98, with the putative RNA helicase gene, DDX10

     Arai Y, et al. · Blood 89(11):3936-3944 1997
     used by NUP98::DDX10, inv(11)(p15q22) — the 'helicase' fusion whose helicase activity turns out not to be the point
117. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 9192636
     Identification of a nuclear matrix targeting signal in the leukemia and bone-related AML/CBF-alpha transcription factors.

     Zeng C, van Wijnen AJ, Stein JL, Meyers S, Sun W, Shopland L, Lawrence JB, Penman S, Lian JB, Stein GS, Hiebert SW · Proceedings of the National Academy of Sciences USA 1997
     used by RUNX1 — activated by KMT2A::AFF1 and then bound by the reciprocal fusion, in the one published two-oncoprotein circuit in t(4;11), RUNX1 — domain architecture and residue coordinates (with the RUNX1b/RUNX1c +27 offset)
118. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 9224939
     A novel SR-related protein specifically interacts with the carboxy-terminal domain (CTD) of RNA polymerase II through a conserved interaction domain.

     Tanner S, Stagljar I, Georgiev O, Schaffner W, Bourquin JP · Biol Chem 1997
     used by SCAF11 / SRrp129 (Q99590) - an SR-related protein that binds the RNA Pol II CTD, in the pan-MLL-fusion core, and alone among the SCAF family
119. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 9150135
     Histone deacetylases and SAP18, a novel polypeptide, are components of a human Sin3 complex.

     Zhang Y, Iratni R, Erdjument-Bromage H, Tempst P, Reinberg D · Cell 1997
     used by SIN3A (Q96ST3) - the scaffold of the OTHER HDAC1/2 corepressor complex, a 5' fusion partner in infant B-ALL and in myelodysplasia, and present in three MLL-fusion AP-MS columns but not the index fusion's, The MLL-fusion interactome recovers corepressor SCAFFOLDS and not their HDAC1/2 catalytic core: NuRD splits 5/7 remodelling arm versus 0/7 deacetylase arm (Fisher p = 0.021), and HDAC1, HDAC2, RBBP4 and RBBP7 are absent from all seven baits
120. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 9162015
     Preferential modification of nuclear proteins by a novel ubiquitin-like molecule.

     Kamitani T, Nguyen HP, Yeh ET · J Biol Chem 1997
     used by SUMO1 - not a complex partner of LEDGF but a modifier of it, and the interactome row cannot tell you which
121. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 9019411
     A small ubiquitin-related polypeptide involved in targeting RanGAP1 to nuclear pore complex protein RanBP2.

     Mahajan R, Delphin C, Guan T, Gerace L et al. · Cell 1997
     used by SUMO1 - not a complex partner of LEDGF but a modifier of it, and the interactome row cannot tell you which
122. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 9292512
     Defects in yolk sac hematopoiesis in Mll-null embryos

     Hess JL, Yu BD, Li B, Hanson R, Korsmeyer SJ · Blood 90(5):1799-1806 1997
     used by The lost SET domain, and the verdict: the fusion is a gain-of-function neomorph, not a KMT2A loss-of-function
123. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 9129043
     The HRX proto-oncogene product is widely expressed in human tissues and localizes to nuclear structures

     Butler LH, et al. · Blood 1997
     used by The MLL-side twin of the 1998 anti-AF4 result: in 1997 the same punctate nuclear pattern was seen with and without an 11q23 translocation, and the authors said so, The soluble-nucleoplasm versus chromatin-bound axis - the one localisation readout that keeps a size dimension, and nobody has run it on a KMT2A fusion
124. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 9233580
     Exon/intron structure of the human AF-4 gene, a member of the AF-4/LAF-4/FMR-2 gene family coding for a nuclear protein with structural alterations in acute leukaemia

     Nilson I, Reichel M, Ennas MG, et al. · British journal of haematology 1997
     used by The other half of the break: what is actually known about the AFF1 breakpoint region, and the negative-control gene nobody cites
125. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 9247190
     Involvement of the rfp tripartite motif in protein-protein interactions and subcellular distribution.

     Cao T, Borden KL, Freemont PS, Etkin LD · J Cell Sci 1997
     used by TRIM27 - the E3 ligase inside PRC1.1 that USP7 spends its time undoing, and the worst UniProt localisation record this graph has audited
126. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 9034339
     A novel ubiquitin-specific protease is dynamically associated with the PML nuclear domain and binds to a herpesvirus regulatory protein.

     Everett RD, Meredith M, Orr A, Cross A, Kathoria M, Parkinson J · EMBO J 1997
     used by USP7 - the enzyme that holds PRC1.1 together, and the only pharmacological handle on this complex that exists today
127. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 8562938
     The human homologue of rat NG2, a chondroitin sulfate proteoglycan, is not expressed on the cell surface of normal hematopoietic cells but is expressed by acute myeloid leukemia blasts from poor-prognosis patients with abnormalities of chromosome band 11q23.

     · Blood 1996
     used by 'Not expressed on normal haematopoietic cells' is a claim about blood, and it has been read for thirty years as a claim about the body, NG2/CSPG4 is the one antigen in the whole surfaceome that KMT2A::AFF1 itself drives - and it is a pericyte and vascular protein, at 124.5 nTPM in normal blood vessel and 246 TPM in tibial artery
128. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 8830039
     The CDw65 monoclonal antibodies VIM-8 and VIM-11 bind to the neutral glycolipid V3FucnLc8Cer.

     Kniep B, Peter-Katalinic J, Muthing J, Majdic O, Pickl WF, Knapp W · J Biochem 1996
     used by A CD number names a reagent cluster, not a molecule - and four different things can sit behind one, CD65 - a neutral glycolipid epitope (V3FucnLc8Cer), no gene, and the CD number that was split in two because its antibodies did not agree, CD65s (VIM-2, sialylated ceramide dodecasaccharide) - the myeloid antigen that, with CD15, makes NG2 a perfect predictor of KMT2A rearrangement
129. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 8634439
     Distribution of 11q23 breakpoints within the MLL breakpoint cluster region in de novo acute leukemia and in treatment-related acute myeloid leukemia: correlation with scaffold attachment regions and topoisomerase II consensus binding sites

     Broeker PL, Super HG, Thirman MJ, Pomykala H, Yonebayashi Y, Tanabe S, Zeleznik-Le N, Rowley JD · Blood 1996
     used by Alu repeats and nuclear-matrix anchors in the KMT2A breakpoint region — the genome-feature side of the break, Analysis: test whether published KMT2A::AFF1 occupancy is enriched at scaffold-attachment and cruciform-prone DNA beyond what CpG islands explain, Each partner prefers a different KMT2A exon: partner-specific break position in 3,401 patients, Hypothesis: KMT2A's AT-hooks are a DNA-topology reader, not an AT-sequence reader — which would link the fusion's address to the scaffold-attachment architecture that also makes its own gene fragile, Prevention by exposure avoidance: verdict NOT FEASIBLE, and the transplacental-exposure literature is much weaker than its prominence suggests, Replication stress, AID, base-excision repair and endonuclease G cut the KMT2A locus, Run in coordinates: the protective CTCF site and the patient break-prone window are ONE element, it is cohesin-bound, and the 'functional cut point' is 3.75 kb away - two of the graph's three exon-11s were the same exon and the third was not, The KMT2A breakpoint cluster region: an 8.3 kb stretch built to break, The three AT-hooks (aa 169-180, 217-227, 301-309) as a localisation determinant — and the correction that MLL's hooks read DNA *structure*, not AT-richness, Topoisomerase II cleavage and TOP2 poisons as a source of KMT2A breaks
130. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 8689683
     Atm-deficient mice: a paradigm of ataxia telangiectasia.

     Barlow C, Hirotsune S, Paylor R, Liyanage M, Eckhaus M, Collins F, Shiloh Y, Crawley JN, Ried T, Tagle D, Wynshaw-Boris A · Cell 1996
     used by ATM - the DNA-damage kinase that phosphorylates three of the four KMT2A 3' partners
131. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 8843195
     The Atr and Atm protein kinases associate with different sites along meiotically pairing chromosomes.

     Keegan KS, Holtzman DA, Plug AW, Christenson ER, Brainerd EE, Flaggs G, Bentley NJ, Taylor EM, Meyn MS, Moss SB, Carr AM, Ashley T, Hoekstra MF · Genes Dev 1996
     used by ATR - the replication-stress kinase with the best preclinical case in this disease and the best published reason not to inhibit it
132. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 8562939
     Human homologue of the rat chondroitin sulfate proteoglycan, NG2, detected by monoclonal antibody 7.1, identifies childhood acute lymphoblastic leukemias with t(4;11)(q21;q23) or t(11;19)(q23;p13) and MLL gene rearrangements.

     Behm FG, ..., Bernstein ID · Blood 1996
     used by CSPG4 / NG2 - the flow-cytometry surrogate for a broken KMT2A, and a direct target gene of the fusion that makes it, MME / CD10 (CALLA) - the marker this disease is defined by NOT having, and the promoter is methylated shut rather than simply not yet switched on, NG2/CSPG4 is the one antigen in the whole surfaceome that KMT2A::AFF1 itself drives - and it is a pericyte and vascular protein, at 124.5 nTPM in normal blood vessel and 246 TPM in tibial artery, Step 1: the blood count and the blood film, Step 2: flow cytometry and the CD10-negative pro-B fingerprint, The immunophenotype beat's own ledger: what was enumerated, what was written, what was dropped and why, and what could not be read
133. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 8636124
     p150TSP, a conserved nuclear phosphoprotein that contains multiple tetratricopeptide repeats and binds specifically to SH2 domains.

     Malek SN, Yang CH, Earnshaw WC, Kozak CA, Desiderio S · J Biol Chem 1996
     used by CTR9 — a PAF1C subunit the field assumes is a fusion partner, with no paper that tested it
134. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 8596958
     An RNA polymerase II elongation factor encoded by the human ELL gene.

     Shilatifard A, Lane WS, Jackson KW, Conaway RC, Conaway JW · Science 1996
     used by ELOA / TCEB3, Elongin A (Q14241) - a Pol II elongation factor in the pan-MLL-fusion core, ALONE, with none of its own complex and a non-zero negative control, KMT2A::ELL (MLL-ELL), t(11;19)(q23;p13.1)
135. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 8563752
     Cooperative activation of Hoxa and Pbx1-related genes in murine myeloid leukaemias

     Nakamura T, Largaespada DA, Shaughnessy JD, Jenkins NA, Copeland NG · Nature Genetics 12:149-153 1996
     used by HOXA7 - the one HOXA paralogue besides HOXA9 with a published loss-of-function requirement for MLL-fusion transformation, and the requirement was shown in vitro only
136. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 8639852
     Molecular analysis of t(11;19) breakpoints in childhood acute leukemias.

     Rubnitz JE, Behm FG, Curcio-Brint AM, Pinheiro RP, et al. · Blood 1996
     used by In childhood t(11;19), every lymphoblastic case was MLLT1 and every ELL case was myeloid - the one rule that lets an old cohort be de-contaminated
137. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 8756581
     Constitutive nuclear localization of Janus kinases 1 and 2.

     Lobie PE, Ronsin B, Silvennoinen O, Haldosén LA, Norstedt G, Morel G · Endocrinology 1996
     used by JAK1 - recruited and stabilised by AF10 fusions, and the kinase whose downstream STAT1 the class I effect of menin inhibition explicitly does not need
138. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 8934541
     Identification of MLL and chimeric MLL gene products involved in 11q23 translocation and possible mechanisms of leukemogenesis by MLL truncation

     Joh T, et al. · Oncogene 1996
     used by Nuclear import of every KMT2A fusion is a property of retained KMT2A sequence, and the determinant was mapped in 1997 to a region containing the AT-hook motifs, The soluble-nucleoplasm versus chromatin-bound axis - the one localisation readout that keeps a size dimension, and nobody has run it on a KMT2A fusion
139. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 8563753
     Fusion of the nucleoporin gene NUP98 to HOXA9 by the chromosome translocation t(7;11)(p15;p15) in human myeloid leukaemia

     Nakamura T, et al. · Nature Genetics 12(2):154-158 1996
     used by NUP98::HOXA9, t(7;11)(p15;p15) — the founding NUP98 fusion, and an incomplete oncogene
140. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 8563754
     The t(7;11)(p15;p15) translocation in acute myeloid leukaemia fuses the genes for nucleoporin NUP98 and class I homeoprotein HOXA9

     Borrow J, et al. · Nature Genetics 12(2):159-167 1996
     used by NUP98::HOXA9, t(7;11)(p15;p15) — the founding NUP98 fusion, and an incomplete oncogene
141. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 8643484
     The t(10;11)(p13;q14) in the U937 cell line results in the fusion of the AF10 gene and CALM, encoding a new member of the AP-3 clathrin assembly protein family.

     Dreyling MH, et al. · Proc Natl Acad Sci U S A 1996
     used by PICALM::MLLT10 (CALM-AF10), t(10;11)(p13;q14) - the DOT1L-dependent HOXA fusion that contains no KMT2A
142. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 8932918
     Maternal exposure to potential inhibitors of DNA topoisomerase II and infant leukemia (United States): a report from the Children's Cancer Group

     Ross JA, Potter JD, Reaman GH, Pendergrass TW, Robison LL · Cancer Causes & Control 1996
     used by Prevention by exposure avoidance: verdict NOT FEASIBLE, and the transplacental-exposure literature is much weaker than its prominence suggests
143. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 8565077
     AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis.

     Okuda T, van Deursen J, Hiebert SW, Grosveld G, Downing JR · Cell 1996
     used by RUNX1 — activated by KMT2A::AFF1 and then bound by the reciprocal fusion, in the one published two-oncoprotein circuit in t(4;11)
144. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 8692929
     The C-terminal domain of the largest subunit of RNA polymerase II interacts with a novel set of serine/arginine-rich proteins.

     Yuryev A, Patturajan M, Litingtung Y, Joshi RV, Gentile C, Gebara M, Corden JL · Proc Natl Acad Sci U S A 1996
     used by SCAF11 / SRrp129 (Q99590) - an SR-related protein that binds the RNA Pol II CTD, in the pan-MLL-fusion core, and alone among the SCAF family
145. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 8679710
     Analysis of foetal expression sites of human type II DNA topoisomerase alpha and beta mRNAs by in situ hybridisation.

     Zandvliet DW, Hanby AM, Austin CA, Marsh KL, Clark IB, Wright NA, et al. · Biochim Biophys Acta 1996
     used by TOP2A - the proliferation isoform, the one the drugs are actually measured against, and the only one with a germline association in this disease, TOP2B - the isoform most etoposide-induced KMT2A breaks depend on, resolved genetically and not resolvable pharmacologically
146. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 8824725
     Distribution of TP53 mutations among acute leukemias with MLL rearrangements.

     Lanza C, Gaidano G, Cimino G, et al. · Genes, Chromosomes and Cancer 1996
     used by TP53 - named in 84 entries of this graph, absent from the index genome study of the disease, and four different things depending on when you look
147. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 8871644
     Multiple types of chimeric germ-line Ig heavy chain transcripts in human B cells: evidence for trans-splicing of human Ig RNA

     Fujieda S, Lin YQ, Saxon A, Zhang K · Journal of Immunology 1996
     used by Trans-splicing: healthy human cells make cancer-associated fusion transcripts without any chromosome rearrangement
148. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 8799830
     Active RNA polymerases are localized within discrete transcription 'factories' in human nuclei

     Iborra FJ, Pombo A, Jackson DA, Cook PR · Journal of Cell Science 1996
     used by Transcription factories and Pol II clusters - no KMT2A::AFF1 imaging, condensate evidence for SEC and MLL-ENL, and 3D-FISH that actively contradicts the factory story for t(4;11)
149. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 8527389
     Complex MLL rearrangement in a patient with T-cell acute lymphoblastic leukemia.

     Chervinsky DS, Sait SN, Nowak NJ, et al. · Genes Chromosomes Cancer 1995
     used by A reciprocal-negative t(11;19) patient was documented in 1995 by a different mechanism entirely - the 3' half of KMT2A was simply deleted, ACER1 is on the list of in-frame reciprocal KMT2A partners - and ACER1 is the gene the 'reciprocal-negative' breakpoints fall next to, The experiment: cross-tabulate MLLT1 breakpoint class against age, lineage and outcome in the Frankfurt archive, then confirm reciprocal status by RNA in whoever has it, The partner-matched control arm is not 241 versus 219 - it is 153 versus 101, and in that subset the two groups make an identical fusion protein
150. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 8618864
     Domains with transcriptional regulatory activity within the ALL1 and AF4 proteins involved in acute leukemia

     Prasad R, Yano T, Sorio C, Nakamura T, Rallapalli R, Gu Y, Leshkowitz D, Croce CM, Canaani E · Proc Natl Acad Sci U S A 92:12160-12164 1995
     used by AFF1 / AF4 — domain architecture and residue coordinates
151. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 7834753
     Multiorgan inflammation and hematopoietic abnormalities in mice with a targeted disruption of RelB, a member of the NF-kappa B/Rel family.

     Weih F, Carrasco D, Durham SK, Barton DS, Rizzo CA, Ryseck RP, et al., Bravo R · Cell 1995
     used by Conventional (myeloid-related) dendritic cell - the DC lineage RELB actually builds, and the thymic part of that phenotype is architecture rather than a cell-intrinsic requirement, RELB — the NF-kB subunit that SUPPRESSES MLL-AF9 leukaemia, with a direct ChIP target list and a genetic rescue, which makes it the best-evidenced anti-leukaemic node in this beat
152. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 7660129
     Elongin (SIII): a multisubunit regulator of elongation by RNA polymerase II.

     Aso T, Lane WS, Conaway JW, Conaway RC · Science 1995
     used by ELOA / TCEB3, Elongin A (Q14241) - a Pol II elongation factor in the pan-MLL-fusion core, ALONE, with none of its own complex and a non-zero negative control
153. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 7761424
     Fusion of the TEL gene on 12p13 to the AML1 gene on 21q22 in acute lymphoblastic leukemia

     Golub TR, Barker GF, Bohlander SK, et al. · PNAS 1995
     used by ETV6 — domain architecture and residue coordinates, ETV6::RUNX1 (TEL-AML1), t(12;21)(p13;q22), RUNX1 — domain architecture and residue coordinates (with the RUNX1b/RUNX1c +27 offset)
154. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 7833491
     Molecular analysis of the Mono Mac 6 cell line: detection of an MLL-AF9 fusion transcript.

     Super HJ, Martinez-Climent J, Rowley JD · Blood 1995
     used by Every human t(9;11) cell line, with every accession fetched and read back: eleven lines, ten patients, and two of them are B-ALL
155. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 7833468
     A novel gene, AF1q, fused to MLL in t(1;11) (q21;q23), is specifically expressed in leukemic and immature hematopoietic cells.

     Tse W, Zhu W, Chen HS, Cohen A · Blood 1995
     used by Experiment: does AF1q self-associate, and does KMT2A::MLLT11 transform? The two measurements nobody has made on the 10th most common KMT2A fusion, KMT2A::MLLT11 (MLL-AF1q), t(1;11)(q21;q23) — 28 patients, and not one functional experiment, MLLT11 / AF1q — a 90-residue protein with no chromatin domain and no oligomerisation module, KMT2A partner in t(1;11)(q21;q23)
156. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 7621074
     Targeted disruption of the flk2/flt3 gene leads to deficiencies in primitive hematopoietic progenitors.

     Mackarehtschian K, Hardin JD, Moore KA, Boast S, Goff SP, Lemischka IR · Immunity 1995
     used by FLT3 / CD135 — the strongest non-tether co-dependency, and a target the field may have written off on a badly executed trial
157. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 7564526
     Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL).

     Bene MC, ..., van't Veer MB · Leukemia 1995
     used by MME / CD10 (CALLA) - the marker this disease is defined by NOT having, and the promoter is methylated shut rather than simply not yet switched on, Step 2: flow cytometry and the CD10-negative pro-B fingerprint
158. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 7938000
     11q23 translocations split the 'AT-hook' cruciform DNA-binding region and the transcriptional repression domain from the activation domain of the mixed-lineage leukemia (MLL) gene

     Zeleznik-Le NJ, Harden AM, Rowley JD · Proceedings of the National Academy of Sciences USA 1994
     used by Analysis: test whether published KMT2A::AFF1 occupancy is enriched at scaffold-attachment and cruciform-prone DNA beyond what CpG islands explain, Chromocentres and pericentromeric satellite heterochromatin — no KMT2A evidence, but the AT-hook argument says there should be, Hypothesis: KMT2A's AT-hooks are a DNA-topology reader, not an AT-sequence reader — which would link the fusion's address to the scaffold-attachment architecture that also makes its own gene fragile, KMT2A / MLL1 — the gene that breaks, KMT2A::AFF1 (MLL-AF4), t(4;11)(q21;q23), Lost from the KMT2A half: the transactivation domain (aa 2829-2883) and its CBP contact, Nuclear matrix and mitotic chromosome scaffold — KMT2A sits with topoisomerase II, in the same place the gene breaks, The three AT-hooks (aa 169-180, 217-227, 301-309) as a localisation determinant — and the correction that MLL's hooks read DNA *structure*, not AT-richness
159. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 8142642
     Detection of fusion transcripts generated by the inversion 16 chromosome in acute myelogenous leukemia

     Claxton DF, Liu P, Hsu HB, et al. · Blood 1994
     used by CBFB — domain architecture and residue coordinates, MYH11 — domain architecture and residue coordinates
160. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 8134107
     A novel gene, AF-1p, fused to HRX in t(1;11)(p32;q23), is not related to AF-4, AF-9 nor ENL

     Bernard OA, Mauchauffe M, Mecucci C, Van den Berghe H, Berger R · Oncogene 1994
     used by EPS15 (AF1p): the EH domains may or may not be discarded, and either way nobody has shown it matters, EPS15 / AF1p — domain architecture, and the one coordinate nobody has published, KMT2A::EPS15 (MLL-AF1p), t(1;11)(p32;q23) — the infant-ALL cytoplasmic partner
161. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 8180386
     A reverse transcriptase-polymerase chain reaction detects heterogeneous chimeric mRNAs in leukemias with 11q23 abnormalities.

     Yamamoto K, Seto M, Iida S, et al. · Blood 1994
     used by Every human t(11;19) KMT2A::MLLT1 cell line, with accessions fetched and read back - and not one of them is known to be reciprocal-negative, Every human t(9;11) cell line, with every accession fetched and read back: eleven lines, ten patients, and two of them are B-ALL, KOPB-26 (CVCL_7972): a t(9;11) B-ALL line from a 13-month-old, and the model for 42% of this partner's patients that nobody uses
162. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 8122112
     Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma

     Morris SW, Kirstein MN, Valentine MB, Dittmer KG, Shapiro DN, Saltman DL, Look AT · Science 1994
     used by Is KMT2A::AFF1 leukemia epithelial or endothelial? No — it is haematopoietic. But the question is a good one, NPM1::ALK (NPM-ALK), t(2;5)(p23;q35)
163. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 8016145
     ALL-1 partial duplication in acute leukemia

     Schichman SA, Caligiuri MA, Gu Y, Strout MP, Canaani E, Bloomfield CD, Croce CM · Proceedings of the National Academy of Sciences USA 1994
     used by KMT2A partial tandem duplication: an addition that only works once the normal copy has been switched off — 'recessive gain-of-function'
164. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 8044771
     ALL-1 tandem duplication in acute myeloid leukemia with a normal karyotype involves homologous recombination between Alu elements

     Schichman SA, Caligiuri MA, Strout MP, Carter SL, Gu Y, Canaani E, Bloomfield CD, Croce CM · Cancer Research 1994
     used by KMT2A partial tandem duplication: an addition that only works once the normal copy has been switched off — 'recessive gain-of-function'
165. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 8058765
     Leucine-zipper dimerization motif encoded by the AF17 gene fused to ALL-1 (MLL) in acute leukemia.

     Prasad R, Leshkowitz D, Gu Y, Alder H, Nakamura T, Saito H, et al. · Proc Natl Acad Sci U S A 1994
     used by KMT2A::MLLT6 (MLL-AF17), t(11;17)(q23;q12-q21) — the bridge case: a leucine zipper on a DOT1L-complex subunit, MLLT6 / AF17 — domain architecture, and where the leucine zipper actually is
166. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 8108440
     The human CAN protein, a putative oncogene product associated with myeloid leukemogenesis, is a nuclear pore complex protein that faces the cytoplasm.

     Kraemer D, Wozniak RW, Blobel G, Radu A · Proc Natl Acad Sci U S A 1994
     used by NUP214 / CAN - the cytoplasmic-face nucleoporin that CRM1 docks against, and the 3' partner of four leukaemia fusions
167. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 8293467
     A novel macromolecular structure is a target of the promyelocyte-retinoic acid receptor oncoprotein

     Dyck JA, Maul GG, Miller WH, Chen JD, Kakizuka A, Evans RM · Cell 1994
     used by PML nuclear bodies and PML::RARA — the best-worked case of a fusion destroying a nuclear compartment, and what it actually predicts for KMT2A
168. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 8293468
     Retinoic acid regulates aberrant nuclear localization of PML-RAR alpha in acute promyelocytic leukemia cells

     Weis K, Rambaud S, Lavau C, Jansen J, Carvalho T, Carmo-Fonseca M, Lamond A, Dejean A · Cell 1994
     used by PML nuclear bodies and PML::RARA — the best-worked case of a fusion destroying a nuclear compartment, and what it actually predicts for KMT2A
169. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 8011967
     Bioavailability and reversible metabolism of prednisone and prednisolone in man.

     Garg V, Jusko WJ · Biopharm Drug Dispos 1994
     used by Prednisone - the prophase drug, the prognostic factor, and a prodrug that has never itself been tested on a KMT2A-rearranged blast
170. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 8199015
     The acute lymphoblastic leukaemia cell line SEM with t(4;11) chromosomal rearrangement is biphenotypic and responsive to interleukin-7

     Greil J, Gramatzki M, Burger R, et al. · British Journal of Haematology 1994
     used by SEM (CVCL_0095) — the workhorse, from a five-year-old, and microsatellite unstable, The eleven-line panel is nine patients, seven of them myeloid, and none an infant
171. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 8080983
     ENL, the gene fused with HRX in t(11;19) leukemias, encodes a nuclear protein with transcriptional activation potential in lymphoid and myeloid cells.

     Rubnitz JE, Morrissey J, Savage PA, Cleary ML · Blood 1994
     used by The KMT2A::MLLT1 chimeric protein: exactly what survives the join on each side, in residue numbers
172. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 7689231
     Acute mixed-lineage leukemia t(4;11)(q21;q23) generates an MLL-AF4 fusion product.

     Domer PH, Fakharzadeh SS, Chen CS, et al. · Proc Natl Acad Sci U S A 1993
     used by Attribution audit 2 of 5 - post-translational modifications on KMT2A::AFF1: nothing survives at peptide level, and the one strong PTM result is explicitly about the wild-type protein, In-silico digest of 81 modelled KMT2A fusion junctions: the peptide that would prove the fusion protein exists, Nuclear import of every KMT2A fusion is a property of retained KMT2A sequence, and the determinant was mapped in 1997 to a region containing the AT-hook motifs, The clustered PHD fingers (KMT2A aa 1416-1640) are a chromatin-targeting module and the canonical t(4;11) junction removes them by ten residues, The five verdicts in one place, plus what this beat read and did not use, The N320-C180 clamp is the only KMT2A module whose disruption has ever been shown to change subnuclear localisation - and the fusion is the disruption, The soluble-nucleoplasm versus chromatin-bound axis - the one localisation readout that keeps a size dimension, and nobody has run it on a KMT2A fusion, The working attribution reagent in this literature is not an antibody, it is the gel - and that single fact predicts which claim classes survive
173. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 8402909
     Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair.

     Veis DJ, Sorenson CM, Shutter JR, Korsmeyer SJ · Cell 1993
     used by BCL2 — the one co-dependency in this beat that already has an approved drug pointed at it
174. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 8402648
     Investigation of the subcellular distribution of the bcl-2 oncoprotein: residence in the nuclear envelope, endoplasmic reticulum, and outer mitochondrial membranes.

     Krajewski S, Tanaka S, Takayama S, Schibler MJ, Fenton W, Reed JC · Cancer Res 1993
     used by BCL2 — the one co-dependency in this beat that already has an approved drug pointed at it
175. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 8351518
     Fusion between transcription factor CBF beta/PEBP2 beta and a myosin heavy chain in acute myeloid leukemia

     Liu P, Tarle SA, Hajra A, et al. · Science 1993
     used by CBFB — domain architecture and residue coordinates, CBFB::MYH11 (CBFbeta-SMMHC), inv(16)(p13;q22), MYH11 — domain architecture and residue coordinates
176. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 8269849
     Expression of relB transcripts during lymphoid organ development: specific expression in dendritic antigen-presenting cells.

     Carrasco D, Ryseck RP, Bravo R · Development 1993
     used by Conventional (myeloid-related) dendritic cell - the DC lineage RELB actually builds, and the thymic part of that phenotype is architecture rather than a cell-intrinsic requirement
177. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 8356452
     Mice lacking TdT: mature animals with an immature lymphocyte repertoire.

     Gilfillan S, Dierich A, Lemeur M, Benoist C, Mathis D · Science 1993
     used by DNTT (TdT) - a real gene the graph calls by its enzyme nickname, and TdT-negativity is 100% KMT2A-rearranged in the largest paediatric series
178. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 8455202
     Report of the Cancer Therapy Evaluation Program monitoring plan for secondary acute myeloid leukemia following treatment with epipodophyllotoxins.

     Smith MA, Rubinstein L, Cazenave L, Ungerleider RS, Maurer HM, Heyn R, et al. · J Natl Cancer Inst 1993
     used by Etoposide (VP-16) - the drug that makes this disease and cures several others, and the only entry in this graph whose main finding is that you must not stop using it
179. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 8344261
     SAR-dependent mobilization of histone H1 by HMG-I/Y in vitro: HMG-I/Y is enriched in H1-depleted chromatin.

     Zhao K, et al. · The EMBO Journal 1993
     used by HMGA1 (P17096) - an AT-hook architectural protein that antagonises histone H1 at scaffold-attachment regions, with a childhood B-ALL relapse correlation that is title-only evidence
180. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.reviewPMID 8215495
     Leukemia cutis in congenital leukemia. Analysis and review of the world literature with report of an additional case

     Resnik KS, Brod BB · Archives of Dermatology 1993
     used by Leukaemia cutis: the skin nodules that can be the first sign of infant leukaemia
181. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 8491376
     LYAR, a novel nucleolar protein with zinc finger DNA-binding motifs, is involved in cell growth regulation.

     Su L, Hershberger RJ, Weissman IL · Genes Dev 1993
     used by LYAR (Q9NX58) - a zinc-finger nucleolar growth regulator cloned from a T-cell leukaemia line, in six of seven MLL-fusion interactomes, and the one member of this block whose discovery system is the same lineage as the AP-MS host
182. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 8497319
     In utero rearrangements in the trithorax-related oncogene in infant leukaemias

     Ford AM, et al. · Nature 1993
     used by Ordering the fusions developmentally — which stage of blood formation each one hijacks, and at what age the child presents, The prevention window: the break happens in a fetus, and we know when it CLOSES but not when it opens, Three pairs of twins who both got leukaemia: the patients who proved the fusion happens before birth, Twin concordance: near-total for infant KMT2A-rearranged leukaemia, about 5% for childhood ALL overall
183. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 8358709
     Heterogeneity in MLL/AF-4 fusion messenger RNA detected by the polymerase chain reaction in t(4;11) acute leukemia

     Hilden JM, Chen CS, Moore R, et al. · Cancer Research 1993
     used by RS4;11 (CVCL_0093) — an ADULT KMT2A::AFF1 line, MSI-high, carrying NSD2 E1099K
184. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 8348613
     Human wee1 maintains mitotic timing by protecting the nucleus from cytoplasmically activated Cdc2 kinase.

     Heald R, McLoughlin M, McKeon F · Cell 1993
     used by WEE1 - the one checkpoint target with a KMT2A::AFF1-specific result, and the paper that also found the escape route
185. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 1423624
     Involvement of a homolog of Drosophila trithorax by 11q23 chromosomal translocations in acute leukemias.

     Tkachuk DC, Kohler S, Cleary ML · Cell 1992
     used by Every human t(11;19) KMT2A::MLLT1 cell line, with accessions fetched and read back - and not one of them is known to be reciprocal-negative, HB11;19 (CVCL_8227) keeps the YEATS domain and expresses both derivative transcripts - so it is the reciprocal-POSITIVE t(11;19) line, and there is no negative one, Nuclear matrix and mitotic chromosome scaffold — KMT2A sits with topoisomerase II, in the same place the gene breaks, The most faithful mouse models of t(11;19) are reciprocal-positive by design, and the commonest ones carry no reciprocal allele at all - and nobody has compared them, The reciprocal MLLT1::KMT2A transcript was reported in the paper that discovered KMT2A, and nobody has gone back to it in thirty-four years
186. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 1465024
     Phenotypic and genotypic characterization of 14 leukemia and lymphoma cell lines with 11q23 translocations.

     Iida S, Saito M, Okazaki T, et al. · Leuk Res 1992
     used by Every human t(9;11) cell line, with every accession fetched and read back: eleven lines, ten patients, and two of them are B-ALL, KOPB-26 (CVCL_7972): a t(9;11) B-ALL line from a 13-month-old, and the model for 42% of this partner's patients that nobody uses
187. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 1522903
     Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours

     Delattre O, Zucman J, Plougastel B, et al. · Nature 1992
     used by EWSR1::FLI1 (EWS-FLI1), t(11;22)(q24;q12)
188. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 1319186
     Primary structure and alternative splice variants of gephyrin, a putative glycine receptor-tubulin linker protein.

     Prior P, Schmitt B, Grenningloh G, Pribilla I, Multhaup G, Beyreuther K, et al. · Neuron 1992
     used by GPHN (gephyrin) — synaptic scaffold and molybdenum-cofactor enzyme, KMT2A fusion partner in t(11;14)(q23;q24)
189. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 1374686
     Molecular cloning and nucleic acid binding properties of the GAP-associated tyrosine phosphoprotein p62.

     Wong G, Müller O, Clark R, Conroy L, Moran MF, Polakis P, McCormick F · Cell 1992
     used by KHDRBS1 (Sam68) — an RNA-binding protein that holds the MLL-AF4 message DOWN, a class no dropout screen can find
190. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 1423592
     The precursor of NF-kappa B p50 has I kappa B-like functions.

     Rice NR, MacKichan ML, Israël A · Cell 1992
     used by NFKB1 (p105/p50) — the only menin-NF-kB subunit with a co-immunoprecipitation, and the arm the MLL leukaemia data points at
191. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 1528853
     HEN1 and HEN2: a subgroup of basic helix-loop-helix genes that are coexpressed in a human neuroblastoma.

     Brown L, Espinosa R, Le Beau MM, Siciliano MJ, Baer R · Proc Natl Acad Sci U S A 1992
     used by NHLH1 / HEN1 / NSCL1 - a TAL1-family bHLH factor found by cross-hybridising with the T-ALL oncogene, whose knockout mouse is normal and whose only imaging call puts it in the GOLGI
192. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 1391946
     Identification of breakpoints in t(8;21) acute myelogenous leukemia and isolation of a fusion transcript, AML1/ETO, with similarity to Drosophila segmentation gene, runt

     Erickson P, Gao J, Chang KS, Look T, Whisenant E, Raimondi S, Lasher R, Trujillo J, Rowley J, Drabkin H · Blood 1992
     used by RUNX1::RUNX1T1 (AML1-ETO), t(8;21)(q22;q22)
193. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 1386162
     Fusion of the leucine zipper gene HLF to the E2A gene in human acute B-lineage leukemia.

     Inaba T, Roberts WM, Shapiro LH, Jolly KW, Raimondi SC, Smith SD, Look AT · Science 1992
     used by TCF3::HLF (E2A-HLF), t(17;19)(q22;p13)
194. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 1437549
     RFP is a DNA binding protein associated with the nuclear matrix.

     Isomura T, Tamiya-Koizumi K, Suzuki M, Yoshida S, Taniguchi M, Matsuyama M, Ishigaki T, Sakuma S, Takahashi M · Nucleic Acids Res 1992
     used by TRIM27 - the E3 ligase inside PRC1.1 that USP7 spends its time undoing, and the worst UniProt localisation record this graph has audited
195. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 1997853
     Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood

     Lipshultz SE, Colan SD, Gelber RD, Perez-Atayde AR, Sallan SE, Sanders SP · New England Journal of Medicine 1991
     used by Anthracycline cardiotoxicity: the heart an infant keeps for sixty years
196. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 1652369
     The PML-RAR alpha fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered RAR

     de The H, Lavau C, Marchio A, Chomienne C, Degos L, Dejean A · Cell 1991
     used by PML::RARA, t(15;17)(q24;q21)
197. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 1827140
     Resolution and characterization of pro-B and pre-pro-B cell stages in normal mouse bone marrow.

     Hardy RR, Carmack CE, Shinton SA, Kemp JD, Hayakawa K · J Exp Med 1991
     used by Pre-pro-B cell (murine Hardy Fraction A) - the stage before pro-B, with germline immunoglobulin genes, and the stage RYBP loss actually removes
198. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 1995093
     NB4, a maturation inducible cell line with t(15;17) marker isolated from a human acute promyelocytic leukemia (M3).

     Lanotte M, Martin-Thouvenin V, Najman S, Balerini P, Valensi F, Berger R · Blood 1991
     used by The unnamed AML lines are NB4 and THP-1 - and NB4 is not KMT2A-rearranged at all
199. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 1651102
     Proliferation- and cell cycle-dependent differences in expression of the 170 kilodalton and 180 kilodalton forms of topoisomerase II in NIH-3T3 cells.

     Woessner RD, Mattern MR, Mirabelli CK, Johnson RK, Drake FH · Cell Growth Differ 1991
     used by TOP2A - the proliferation isoform, the one the drugs are actually measured against, and the only one with a germline association in this disease, TOP2B - the isoform most etoposide-induced KMT2A breaks depend on, resolved genetically and not resolvable pharmacologically
200. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 2408149
     Tyrosine kinase activity and transformation potency of bcr-abl oncogene products

     Lugo TG, Pendergast AM, Muller AJ, Witte ON · Science 1990
     used by BCR::ABL1 (Philadelphia chromosome), t(9;22)(q34;q11)
201. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 1690317
     Distribution of VIM-2 and SSEA-1 glycoconjugate epitopes among human leukocytes and leukemia cells.

     Macher BA, Beckstead JH · Leuk Res 1990
     used by CD15 (Lewis-x, SSEA-1, 3-fucosyl-N-acetyllactosamine) - a sugar, not a protein: the most-named antigen in this graph that no gene encodes, CD65 - a neutral glycolipid epitope (V3FucnLc8Cer), no gene, and the CD number that was split in two because its antibodies did not agree
202. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 1692833
     The A.T-DNA-binding domain of mammalian high mobility group I chromosomal proteins. A novel peptide motif for recognizing DNA structure

     Reeves R, Nissen MS · Journal of Biological Chemistry 1990
     used by Experiment: a topology-controlled binding survey of the MLL AT-hook region, plus a triple AT-hook alanine mutant in an endogenously tagged fusion, Hypothesis: KMT2A's AT-hooks are a DNA-topology reader, not an AT-sequence reader — which would link the fusion's address to the scaffold-attachment architecture that also makes its own gene fragile, The three AT-hooks (aa 169-180, 217-227, 301-309) as a localisation determinant — and the correction that MLL's hooks read DNA *structure*, not AT-richness
203. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 1967982
     Chromosomal translocation t(1;19) results in synthesis of a homeobox fusion mRNA that codes for a potential chimeric transcription factor

     Nourse J, Mellentin JD, Galili N, et al. · Cell 1990
     used by PBX1 — domain architecture and residue coordinates, TCF3 (E2A) — domain architecture and residue coordinates, TCF3::PBX1 (E2A-PBX1), t(1;19)(q23;p13.3)
204. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 2491958
     Phase I and pharmacokinetic evaluation of thiotepa in the cerebrospinal fluid and plasma of pediatric patients: evidence for dose-dependent plasma clearance of thiotepa.

     Heideman RL, Cole DE, Balis F, Sato J, Reaman GH, Packer RJ, Singher LJ, Ettinger LJ, et al. · Cancer Research 1989
     used by Thiotepa - the third agent that reaches the central nervous system completely, and whose alkylating metabolites are excreted through the skin into a nappy
205. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 3165295
     Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia

     Huang ME, Ye YC, Chen SR, Chai JR, Lu JX, Zhoa L, Gu LJ, Wang ZY · Blood 1988
     used by PML::RARA, t(15;17)(q24;q21)
206. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 2989703
     Structural organization of the bcr gene and its role in the Ph' translocation

     Heisterkamp N, Stam K, Groffen J, de Klein A, Grosveld G · Nature 1985
     used by BCR::ABL1 (Philadelphia chromosome), t(9;22)(q34;q11)
207. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 3862359
     Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French-American-British Cooperative Group

     Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, Sultan C · Annals of Internal Medicine 1985
     used by Monoblast — the immature monocyte that names FAB M5a, the dominant morphology of congenital KMT2A leukaemia, Monocyte — the graph's most-discussed undefined cell identity, and the confound sitting under its own DepMap haem signal
208. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 6970727
     Establishment and characterization of a human acute monocytic leukemia cell line (THP-1).

     Tsuchiya S, Yamabe M, Yamaguchi Y, et al. · Int J Cancer 1980
     used by THP-1 (CVCL_0006): the default KMT2A::MLLT3 line, from a one-year-old, carrying NRAS G12D and a TP53 frameshift
209. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 4126434
     A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining

     Rowley JD · Nature 1973
     used by What is a fusion gene?
210. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.dataset
     analyses/q181-is-the-epigenetics-gap-real/{baserate.py,keys.py} - phrase scan over data{} across all 3,032 node files and full key enumeration over the 541-entry gene/protein population, commit ac2aeab, 2026-09-24
     used by 124 entries already write NOT APPLICABLE as a category statement on the localization dimension, and the epigenetics dimension has no equivalent - so a correctly-annotated Golgi enzyme and an unwritten chromatin protein are indistinguishable in the epigenetics figure, 42.5% of every node in this corpus names a histone mark, so 'names a mark' is a weak instrument - but it is not noise, and the two types where it collapses are the ones that tell you it is measuring something, Against a chromatin-machinery name list written before the intersection, only 8 of 151 symbols have an entry with no mark, no epigenetics field and no chromatin concept at all - and 7 of the 8 are the P-TEFb brake and the AFF paralogues, Chromatin accessibility is named in the PI's own dimension and the detector has no token for it - nor for enhancer, nucleosome, Polycomb or remodelling - so 121 of the 195 entries scored as having nothing do name a chromatin concept, Epigenetics reads 39.2% and looks like the thinnest PI dimension. Roughly half of the shortfall is a missing FIELD NAME over content that is already there, a third is proteins with no chromatin context to record, and the real content gap is about a ninth of the corpus, Every PI-dimension coverage line in this project is two-valued, and a third of what it counts as missing is a state the metric has no way to express - so the epigenetics figure will not improve by filling fields, and should not be made to, Every WRAD subunit, DOT1L, ENL, AF9 and LEDGF carries a cited histone-mark finding and none carries an epigenetics field - 12 of the 32 index-fusion core proteins are pure notation gaps, 9 are covered, and the 11 with nothing are all on the negative-regulatory side of elongation, RUN (by the King, cycle 159): the eight definitions span 55 points, from 36.8% to 78.8% on one population - every pre-registered reading fires, the beat is NOT refuted, and bare 'chromatin' alone moves it 25 points, The epigenetics coverage test inspects data{} KEY NAMES and never a field's value, so 71 entries that state a histone mark INSIDE a data field score zero - and four more are missed by one character
211. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     analyses/source-independence-by-lab/run.py re-run 2026-09-22; union-find over PubMed author lists, papers merged on a folded last author or >=3 shared authors; written to result.json and, from this cycle, also to results.json
     used by 3,288 papers are 2,025 research groups, the per-entry overcount is 11.7% and barely moved while the graph doubled - and TWO entries now rest on three papers from a single laboratory, where the first run of this analysis found none
212. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.
     analyses/do-the-unverified-citations-support-their-claims - ranked low scorers and their adjudication
     used by A claim-to-paper overlap score measures where a citation's support lives, not whether it exists - so its zero is a pointer to a supplement, not a verdict against the citation, The check this project named nine cycles ago and never ran: the 34 least-verified papers in the corpus are attached to the right claims, and every low-scoring pair is support living in a supplement or a structure rather than an abstract
213. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.
     analyses/depmap-kmt2a-selective-scan-full/run.py, lines 156-180, read directly from the committed source
     used by A real defect in a committed scan, computed three days ago and never written up: `depmap-kmt2a-selective-scan-full` fixes both comparison arms from the FIRST gene that returns data, so five of sixteen eligible KMT2A-rearranged lines are excluded from all 17,728 gene comparisons - including the genes where they were screened, The HBO1/MOZ modules are not selective as modules: one paralogue per family carries the signal, and no member clears both a dependency and a pan-essentiality bar
214. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.
     analyses/depmap-scan-line-identities/results.json - re-runs only the line-resolution step of the source scan and persists the identities the scan discarded
     used by A real defect in a committed scan, computed three days ago and never written up: `depmap-kmt2a-selective-scan-full` fixes both comparison arms from the FIRST gene that returns data, so five of sixteen eligible KMT2A-rearranged lines are excluded from all 17,728 gene comparisons - including the genes where they were screened
215. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.analysis
     Per-bait obligate-partner matrix and chance-expectation null, run 2026-09-21: analyses/obligate-partner-test/run_per_bait_and_null.py over Skucha 2018 Supplementary Table 5, scoring all 13 pairs in each of the seven bait columns and computing 1-(1-960/B)^m across three backgrounds (20,431 / 5,754 / 4,600).
     used by A sharper test than complex enrichment: is the claimed partner's OBLIGATE partner also there? — and its fourth failure is the one protein the source paper named as its own non-selectivity control
216. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.analysis
     Per-partner obligate-partner scoring with an exact binomial upper tail, run 2026-09-21: analyses/obligate-partner-test/run_per_partner.py over Skucha 2018 Supplementary Table 5, one Bernoulli trial per named obligate partner against p0 = 960/B for B in {20431, 5754, 4600}.
     used by A sharper test than complex enrichment: is the claimed partner's OBLIGATE partner also there? — and its fourth failure is the one protein the source paper named as its own non-selectivity control
217. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.
     analyses/which-computed-results-were-never-written-up - directory-level sweep of every analysis output against every node file
     used by A sweep for the failure that cost two cycles: of 234 analysis directories holding a non-empty results file, only 5 are cited by no entry at all - so the backlog is real but small, and one of the five contains a defect in a committed scan
218. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.dataset
     analyses/q189-is-aff1-peptide-poor-or-is-the-threshold-broken/run.py and results.json - in-silico fully-tryptic digest of UniProt sequences fetched from the UniProt REST API, 2026-09-24
     used by AFF1 is NOT peptide-poor - it yields 49 detectable tryptic peptides against menin's 28, and menin cleared the identity threshold while AFF1 scored zero - but the two groups do not separate on peptide yield at all, so the driver is abundance, DDX6 - the only protein ever proposed to do for a cell what Tat does for the virus, on the strength of one 2016 paper, Directed extraction of P-TEFb from the reservoir: HIV-1 Tat is the worked example, and the only cellular candidate rests on one unreplicated paper, KMT2A::AFF1 (MLL-AF4), t(4;11)(q21;q23), KMT2A::AFF1 cells run with more free P-TEFb than other leukaemias - and if they do not, this graph's CDK9 story is about recruitment only, Raising HEXIM1 to brake the fusion's output without touching the fusion - one supporting experiment, one chemical series, and no therapeutic window, The AFF-family N-terminus on cyclin T1: Kd 10 nM, a 2.94 A crystal, and every number in it measured on AFF4 rather than on AFF1, The fusion begins at AFF1 residue 347 and the cyclin T1-binding sequence ends at 308, so KMT2A::AFF1 is the one AFF-family protein that cannot enter the reservoir, The index fusion DISCARDS the SIAH degron: the junction is at AFF1 residue 347, the degron is at human 282-304, and three entries had it the other way because they measured a murine motif against an exon-numbering junction, The two t(4;11) products split AFF1 exactly at the P-TEFb-binding module, and the elongation half goes to the reciprocal
219. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
     IntAct fusion-construct census, run 2026-09-22: analyses/intact-fusion-construct-census/run.py against the EBI IntAct REST findInteractor endpoint, 22 queries, followed by direct findInteractions interrogation of each new candidate.
     used by Asking IntAct for its own fusion constructs found a sixth, exposed a duplicate record that would have inflated the count by three, and failed its own control 4 of 5 - so the floor is lower, not closed
220. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
     IntAct findInteractions interrogation of EBI-9513644, EBI-1157918 and EBI-11579188, run 2026-09-22, with partner-to-interaction-ac mapping recomputed from analyses/intact-fusion-construct-interactors/results.json after the enumeration was re-run with six constructs and (interaction ac, partner) deduplication.
     used by Asking IntAct for its own fusion constructs found a sixth, exposed a duplicate record that would have inflated the count by three, and failed its own control 4 of 5 - so the floor is lower, not closed
221. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.
     analyses/does-full-text-explain-the-low-overlap-scores/results.json - supplement reachability census with three outcomes per file (RETRIEVED / NOT_A_FILE / UNREACHABLE)
     used by Bounded unreachable: the Blood supplemental table that three entries read their NLRC5 and CIITA group assignments from cannot be retrieved by ANY programmatic route - PMC serves a landing page and the publisher 403s this client - so those claims are re-readable but not re-verifiable without a human's institutional access, U4 was assumed, so I tested it: full text raises the low claim-to-paper overlap scores with a +0.108 median margin over same-field decoys (42% of the raw rise is document length), and every one of the seven pairs that stays low is a blind spot in my own instrument rather than a misattached citation
222. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     UniProtKB entry Q86X55 (CARM1_HUMAN), retrieved by gene_exact:CARM1 AND organism_id:9606 AND reviewed:true with fields accession, id, protein_name, gene_names, length, cc_subcellular_location, ft_domain, cc_function, cc_tissue_specificity; fetched 2026-09-22 with the record count asserted as exactly one before use
     used by CARM1 / PRMT4 (Q86X55) - the H3R17me2a writer, and the enzyme whose product is read by the KMT2A C-terminus that every fusion deletes
223. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
     NCBI esearch against PubMed with ID sets compared at retmax=1200, 2026-09-22; every zero checked for a non-empty querytranslation and a warninglist entry before being recorded
     used by CARM1 / PRMT4 (Q86X55) - the H3R17me2a writer, and the enzyme whose product is read by the KMT2A C-terminus that every fusion deletes
224. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.dataset
     scripts/check-pi-dimensions.py lines 69-72 (the _EPI_MARK definition) and analyses/q181-is-the-epigenetics-gap-real/vocab.py, 2026-09-24
     used by Chromatin accessibility is named in the PI's own dimension and the detector has no token for it - nor for enhancer, nucleosome, Polycomb or remodelling - so 121 of the 195 entries scored as having nothing do name a chromatin concept, Epigenetics reads 39.2% and looks like the thinnest PI dimension. Roughly half of the shortfall is a missing FIELD NAME over content that is already there, a third is proteins with no chromatin context to record, and the real content gap is about a ninth of the corpus, Every PI-dimension coverage line in this project is two-valued, and a third of what it counts as missing is a state the metric has no way to express - so the epigenetics figure will not improve by filling fields, and should not be made to
225. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.
     Human Protein Atlas consensus tissue RNA (nTPM) via the search_download API; analyses/hpa-normal-tissue-surface-antigens
     used by CSPG4/NG2 is 0.0 nTPM in normal bone marrow, so the ratio metric is undefined for it - and that zero is the favourable half of its profile, which a ratio-ranked table hides entirely, Excluding spleen, lymph node and thymus moves 9 of 29 normal-tissue safety ratios and not one of the worst cases - the artefact is real, concentrated and confined to the middle of the table, and it takes the ACTB reference down with it, LAMP5, a surface antigen this project named as a fusion-enriched candidate, is 19.6x higher in normal cerebral cortex than in bone marrow - worse than every one of the 22 chromatin targets previously scored, including MEIS1, Where else in a child is the target switched on? (run)
226. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     UniProtKB entry Q08211 (DHX9_HUMAN), retrieved by gene_exact:DHX9 AND organism_id:9606 AND reviewed:true with fields accession, id, protein_name, gene_names, length, cc_subcellular_location, ft_domain, cc_function, fetched 2026-09-22 (exactly one reviewed result)
     used by DHX9 / RNA helicase A (Q08211) - the other TDRD3 effector, and it is itself the 3' partner of a leukaemia fusion
227. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
     NCBI esearch against PubMed with ID sets compared at retmax=500, 2026-09-22; querytranslation and warninglist recorded for the zero.
     used by DHX9 / RNA helicase A (Q08211) - the other TDRD3 effector, and it is itself the 3' partner of a leukaemia fusion
228. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.analysis
     Core-complex interactome gap, re-run 2026-09-21: analyses/core-complex-interactome-gap/run.py against IntAct's curated interactors of KMT2A, MEN1, PSIP1, AFF4, DOT1L and AFF1, counting an entry only where a node IS that protein (gene-<symbol>, protein-<symbol> or protein-<symbol>-domains).
     used by Diffing the core scaffold's curated interactome against the graph: 46 of 217 partners are things here, CDK9 is not one of them, and the filter I built to rank the rest was counting one platform twice, Twenty-five of thirty-six analyses that measure this graph were computed against a graph that no longer exists, and seven stamp a date that never moves
229. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
     ENCODE experiment ENCSR000AKW, K562 H3K9me1 histone ChIP-seq (Bradley Bernstein lab, Broad); files ENCFF271KWX and ENCFF654SLZ, fold change over control, GRCh38; read by HTTP range request 2026-09-22
     used by H3K9me1 depletion over the KMT2A breakpoint cluster replicates in a leukaemia line - as a broad-domain property of the 7.5 kb BCR, not of the 1 kb CTCF element, where the two tracks disagree in sign, The KMT2A locus sits inside a 179-318 kb H3K9me2-domain-free block in human CD34+ bone-marrow progenitors - the 7th, 11th and 37th longest such block on chr11 in three ChIPs - and the same block is present in granulocytes, K562 and most primary AML
230. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     UniProtKB entry P17096 (HMGA1_HUMAN), retrieved by gene_exact:HMGA1 AND organism_id:9606 AND reviewed:true with the reviewed-record count asserted as exactly one before use; fetched 2026-09-22
     used by HMGA1 (P17096) - an AT-hook architectural protein that antagonises histone H1 at scaffold-attachment regions, with a childhood B-ALL relapse correlation that is title-only evidence
231. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
     IntAct fusion-construct interactor enumeration, run 2026-09-22: analyses/intact-fusion-construct-interactors/run.py against the EBI IntAct REST findInteractions endpoint, paging all interactions of four fusion-construct interactor ids and diffing the resolved partner symbols against the node corpus.
     used by IntAct holds 51 interaction records whose participant IS a KMT2A fusion across 6 constructs, our coverage instrument dropped every one of them silently, and closing the single gap they contained took the partner list to 21 of 21
232. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
     UniProtKB Q93052 (LPP_HUMAN), Lipoma-preferred partner - queried as gene_exact:LPP AND organism_id:9606 AND reviewed:true, which returned exactly one reviewed record
     used by LPP (lipoma-preferred partner) - a KMT2A fusion partner in acute monoblastic leukaemia whose day job is adhesion mechanotransduction, and which is barely expressed in leukocytes
233. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
     NCBI E-utilities esearch/efetch against PubMed, 2026-09-22: LPP[tiab] n=4215 with 60 relevance-ranked records classified by hand; 'lipoma-preferred partner'[tiab] n=64; LPP[tiab] AND leukemia[tiab] n=12; LPP[tiab] AND (MLL[tiab] OR KMT2A[tiab]) n=3
     used by LPP (lipoma-preferred partner) - a KMT2A fusion partner in acute monoblastic leukaemia whose day job is adhesion mechanotransduction, and which is barely expressed in leukocytes
234. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
     NCBI esearch against PubMed, 2026-09-22, with querytranslation and warninglist recorded for every zero and both load-bearing zeros re-run.
     used by Menin inhibition collapses the serine/one-carbon/ASNS programme in KMT2A::AFF1 cells - PHGDH -3.24, PSAT1 -2.40, ASNS -1.72, flat in a wild-type line - so it should re-sensitise KMT2A-rearranged ALL to asparaginase, a combination PubMed has zero records for
235. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     Expression-floor sweep over the cached GSE63664 sample tables for SEM, RS4;11 and REH, computed in analyses/was-the-weak-inhibitor-doing-the-same-thing-weakly/run.py, field cycle_55_selectivity_retested_under_expression_floors.
     used by MI-2-2 was doing a weak version of the same thing - 5.8x enriched overlap with the potent inhibitor, 75% concordant - and the selectivity claim it left behind gets STRONGER when low-expressed probes are filtered out, 9.6x to 22.1x, SUPERSEDED IN PART, CYCLE 56 - the MI-2-2 response is ~9x fusion-selective (that stands), but 'does not touch HOXA or MEIS1' was a fact about a weak compound: VTP-50469 collapses MEIS1 -5.25 log2 in the same line, The 24 genes that respond to BOTH menin inhibitors in RS4;11 are led by the ATF4 stress programme - CHAC1 -5.11, STC2 -4.40, TRIB3 -3.10 - and CHAC1 and TRIB3 are named zero times in this graph, The serine/one-carbon arm is NOT a pure ATF4 output: it is menin-selective where the ISR arm is compound-independent (median margin -0.55 vs -0.02, p=0.011), and it is ABSENT in KMT2A::MLLT3 AML where the ISR arm is present
236. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
     ClinicalTrials.gov API v2 /studies, query.intr over nine menin-inhibitor names, deduplicated by NCT id and scanned over outcomesModule primary/secondary/other measure and description fields; retrieved 2026-09-22
     used by No menin-inhibitor trial measures homocysteine or any amino-acid endpoint across 57 records - while a recruiting infant-ALL trial already gives PEG asparaginase and ziftomenib together
237. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
     ClinicalTrials.gov API v2 individual study records for NCT05848687, NCT05761171 and NCT07636564, retrieved and read individually 2026-09-22; intervention lists taken from armsInterventionsModule and age ranges from eligibilityModule
     used by No menin-inhibitor trial measures homocysteine or any amino-acid endpoint across 57 records - while a recruiting infant-ALL trial already gives PEG asparaginase and ziftomenib together
238. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
     analyses/how-much-of-the-named-but-unwritten-queue-is-a-different-word/run.py and results.json, run over data/graph/nodes/*/*.json on 2026-09-22 against the HGNC complete set cached at analyses/depmap-null-distribution/hgnc_complete_set.txt; the script asserts the HGNC parse returned more than 15,000 symbols and that it walked more than 2,000 node files before reporting
     used by No name-based test can clear a gene symbol, and GAPDH is the proof: 48 files, zero name support, unambiguously the real gene - so the triage is one-sided, 145 REAL and 144 ABSTAIN, No two entries name the same gene - 574 symbol-shaped entries, zero duplicate groups - and only two use a symbol HGNC does not approve: gene-kdm3c is JMJD1C and gene-bod1l is BOD1L1, The 'named but unwritten' queue flags ALL EIGHT of this project's negative-control loci plus one alias-filed entry - 20.5% of it, after I corrected my own reimplementation which had double-counted collisions the tool already blocks
239. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
     Cellosaurus REST API (api.cellosaurus.org/search/cell-line), queried 2026-09-21: cc:"KMT2A" with rows=1000 returning 592 lines scored by disease-list, plus di:"Sclerosing epithelioid fibrosarcoma" and three fusion-level cc: queries.
     used by Nobody has ever asked whether a KMT2A-rearranged sarcoma needs menin: zero records, and the reason is that no model exists
240. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
     NCBI esearch against PubMed with ID sets compared at retmax=900, 2026-09-22; every zero checked for a non-empty querytranslation and a warninglist entry before being recorded as a zero
     used by NUCKS1 (Q9H1E3) - a RAD51AP1 paralogue that binds the same DNA with weaker affinity, and whose measured phenotype is mitomycin-C sensitivity rather than the D-loop binding this graph reached for
241. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     UniProtKB entry Q14980 (NUMA1_HUMAN), retrieved by gene_exact:NUMA1 AND organism_id:9606 AND reviewed:true with fields accession, id, protein_name, gene_names, length, cc_subcellular_location, ft_domain, cc_function, cc_disease, cc_tissue_specificity; fetched 2026-09-22, exactly one reviewed result returned and asserted before use
     used by NUMA1 / NuMA (Q14980) - a nuclear-matrix protein that becomes the spindle pole, and the 5' partner of a variant APL fusion whose coiled-coil is required for oncogenicity
242. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
     NCBI esearch against PubMed, ID sets compared at retmax=600, 2026-09-22; every zero checked for a non-empty querytranslation and a warninglist entry before being recorded as a zero
     used by NUMA1 / NuMA (Q14980) - a nuclear-matrix protein that becomes the spindle pole, and the 5' partner of a variant APL fusion whose coiled-coil is required for oncogenicity
243. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
     ClinicalTrials.gov API v2, query.intr over revumenib, SNDX-5613, ziftomenib, KO-539, bleximenib, JNJ-75276617, DSP-5336, enzomenib and BMF-219, deduplicated by NCT id and scanned whole-record, 2026-09-22; the script asserts a control token matched before any zero is reported
     used by NUP98 is an eligibility criterion in 22 of 57 menin-inhibitor trials including a paediatric trial for that genotype alone - and NSD1 and KDM5A appear in none of them, so trials select on the fusion and never on its partner
244. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.
     Human Protein Atlas consensus tissue RNA (nTPM) via the search_download API; analyses/hpa-normal-tissue-surface-antigens
     used by PROM1/CD133 is 5.27x higher in normal kidney than in bone marrow - worse than MEN1 on this project's own safety metric - and it was absent from the filter because that filter scored 22 chromatin targets and not one surface antigen
245. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.
     coordinator computation from C:/Temp/q147part/promoter_matrix.tsv against the 4,191-window census persisted by analyses/q153-can-an-irx2-promoter-measurement-be-attributed
     used by Q153's named threat, run: the reciprocal KMT2A-C arm shows the same bidirectional-promoter enrichment as the fusion-side N arm (44.86% against 43.86%), and IgG shows 33.86% - so the 2.03x is mostly accessibility, carries a real 7-point KMT2A-family component, and is not fusion-specific in any part
246. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     KMT2A CDS and domain map, this graph's own instrument: ana-kmt2a-exon-to-domain-map, derived and verified against Ensembl ENST00000534358 (36 exons, 3,972 aa)
     used by Seven KMT2A-rearranged sarcomas retain the menin-binding motif, three of them carry the complete leukaemic N-terminal module, and all sixteen partner names were in one unopened supplementary table, The KMT2A breakpoint cluster region in base positions: three incompatible definitions reconciled to one GRCh38 table, with the DCAL frame's three bp identities re-derived and the GRCh37 lift measured per interval
247. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     UniProtKB entry P23246 (SFPQ_HUMAN), fields accession, protein_name, gene_names, length, mass, cc_subcellular_location, ft_domain, ft_region, fetched 2026-09-22
     used by SFPQ / PSF (P23246) - the last of 21 fusion-construct partners without an entry, and it is itself the 5' half of an ALL fusion that puts ABL1 in the nucleus
248. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     Cellosaurus records CVCL_0095 (SEM), CVCL_0093 (RS4;11) and CVCL_1650 (Reh), fetched by accession 2026-09-22 via api.cellosaurus.org with the identifier read back, cross-checked against this graph's line-sem-kmt2a-aff1 entry.
     used by SUPERSEDED IN PART, CYCLE 56 - the MI-2-2 response is ~9x fusion-selective (that stands), but 'does not touch HOXA or MEIS1' was a fact about a weak compound: VTP-50469 collapses MEIS1 -5.25 log2 in the same line
249. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     UniProtKB entry Q9H7E2 (TDRD3_HUMAN), fields accession, protein_name, gene_names, length, cc_subcellular_location, ft_domain, fetched 2026-09-22
     used by TDRD3 (Q9H7E2) - the reader the new H4R3me2a entry could not name, and it brings TOP3B to the MYC promoter and keeps R loops off it
250. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
     NCBI esearch against PubMed, 2026-09-22, with querytranslation and warninglist recorded for each zero; corpus counts by direct grep over data/graph/nodes.
     used by TDRD3 (Q9H7E2) - the reader the new H4R3me2a entry could not name, and it brings TOP3B to the MYC promoter and keeps R loops off it
251. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.
     analyses/q152-the-aff1-only-recurrent-promoter-core - label-permutation null over the occupancy matrix, independently re-run by the coordinator
     used by The 332 AFF1-only promoters are BELOW chance: a label-permutation null over the same occupancy matrix expects 426, so the figure the IRX1 partner-specificity line rests on is not an enrichment - and my own brief told the agent the opposite
252. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.journal-articlePMID 32296183
     Luck K et al., A reference map of the human binary protein interactome, Nature 2020;580(7803):402-408 - and the six further records listed in the claim, each fetched from PubMed on 2026-09-24
     used by The atlas heuristic is scoped to six baits instead of to publication scale, so it misses HuRI, OpenCell and five other proteome-wide screens - 49.5% of rows credited with a 'focused' publication have only atlas support, and all five of q178's credible interactors fail
253. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.source-code
     scripts/is-symbol-covered.py line 359 (exact `pre + sl in ids` match) against the live node-id set, counted 2026-09-24
     used by The coverage tool's id arm cannot reach five of its nine prefixes - 225 entries - and the prose arm covers for it in 338 of 338 cases, so the reported false clear happens only under a flag that disables the prose arm
254. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.
     analyses/q150-the-authors-intervals-and-the-depth-matched-discriminator - pre-registered interval scoring and binomial-thinning depth match on GSE252378
     used by The depth-matched discriminator I called the only available test: thinning 44 of 54 libraries down to A73051's in-promoter fragment count moves their oncoprotein share by a median of +0.0003, 39 of 39 hold and 0 collapse - so depth could never have explained A73051, and my cycle-135 worry was misconceived rather than merely wrong, The measurement q148 called the one thing that could overturn its headline: scored as ~20 kb intervals instead of 2 kb promoters, the authors' GMP-like class is enriched in 0 of 24 untreated non-circular samples, while the two control classes reach 19 and 10 - so the promoter window was not the limitation
255. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     Side-by-side of analyses/gse63664-menin-inhibitor-sem-versus-wildtype/results.json (MI-2-2, Affymetrix GPL570) against analyses/vtp50469-does-it-collapse-hoxa-where-mi22-did-not/results.json (VTP-50469, 3'-end RNA-seq), both read from disk 2026-09-22, restricted to the shared cell line RS4;11 and the gene panel declared in the earlier script.
     used by The experiment that refutes cycle 55's headline was already public: VTP-50469 collapses MEIS1 32-fold in the same line where MI-2-2 left it untouched - and HOXA9 was never actually measured by either dataset, The gain question is answerable today for free: GSE127508 contains MLL1n ChIP-seq in a fusion-only line, plus and minus VTP-50469, and nobody has called peaks on the treated sample, The serine/one-carbon arm is NOT a pure ATF4 output: it is menin-selective where the ISR arm is compound-independent (median margin -0.55 vs -0.02, p=0.011), and it is ABSENT in KMT2A::MLLT3 AML where the ISR arm is present
256. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
     Per-gene DMSO baselines from analyses/vtp50469-does-it-collapse-hoxa-where-mi22-did-not/results.json, field the_test, together with the GPL570 probe audit in analyses/gse63664-menin-inhibitor-sem-versus-wildtype/results.json, field hoxa9_every_probe_mentioning_it.
     used by The experiment that refutes cycle 55's headline was already public: VTP-50469 collapses MEIS1 32-fold in the same line where MI-2-2 left it untouched - and HOXA9 was never actually measured by either dataset
257. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     UniProtKB REST, gene_exact:<SYMBOL> AND organism_id:9606 AND reviewed:true, fields accession/id/protein_name/gene_names/length, one symbol per request with the record count asserted before use; fetched 2026-09-22
     used by The histone/ribosomal shape in the read queue is three classes, not one - H2BC21 is distinguishable AND essential at -0.70, so neither existing rejection ground reaches it, and HMGA1 is a harder dependency than MEN1 or KMT2A
258. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     analyses/interactome-union-migrated-to-rest/results.json, field recovered_from_accession; accessions resolved at UniProt REST with primaryAccession compared before the symbol was accepted, 2026-09-22
     used by The interactome instrument is migrated to IntAct REST: 277 partners, 118 written, 42.6% - the denominator grew by 60 and coverage fell 3.5 points, which is the instrument getting honest
259. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.
     analyses/is-the-full-text-rise-just-document-length - pre-registered same-field decoy control on the cycle-133 full-text scores
     used by The length-matched control I demanded of myself: 42% of the abstract-to-full-text rise is reproduced by an unrelated same-field paper, so the specificity I claimed for it was roughly half what I reported
260. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.
     Human Protein Atlas consensus tissue RNA (nTPM) via the search_download API; analyses/hpa-normal-tissue-surface-antigens
     used by The leukocyte artefact runs the opposite way to the one I pre-registered: it makes a haematopoietic antigen look dangerous by loading spleen and lymph node, and the fix is to read which tissue carries the signal rather than how big the ratio is
261. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.dataset
     UCSC Genome Browser hg38 ncbiRefSeqCurated table, downloaded 2026-09-24 (HTTP 200, 4,801,131 bytes); joined against C:/Temp/q145irx1/promoters.tsv (19,404 rows, refGene snapshot dataTime 2020-08-17)
     used by The promoter table's second blind spot is not annotation drift at 1.8% - it is one row per symbol at 14.7%, and the case that motivated the question is not displaced at all
262. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     Panel comparison between analyses/mv411-third-aff1-line-independent-lab-asns-replication/results.json and analyses/vtp50469-does-it-collapse-hoxa-where-mi22-did-not/results.json, both read from disk 2026-09-22, restricted to genes expressed above floor in the MV4;11 Safe3 DMSO arm.
     used by The serine arm replicates in a third KMT2A::AFF1 line from an independent laboratory - PHGDH -2.77, PSAT1 -2.17, GPT2 -2.34, ASNS -1.16 - but the ISR output genes do not, and it survives PCGF1 and BCOR knockout, The washout data cannot say whether the serine/ASNS collapse is durable - the washout control never recovers, ASNS is undetectable in the line, and the housekeeping drifts in opposite directions in the two matrices, Three unnamed things at once: the DOT1L-PRC1.1 deposition names the fusion, the cell types and both inhibitors with concentrations
263. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     UniProtKB REST, gene_exact:<SYMBOL> AND organism_id:9606 AND reviewed:true with fields accession, id, protein_name, gene_names, length, cc_subcellular_location, cc_function, cc_tissue_specificity; one symbol per request with the reviewed-record count asserted as exactly one; fetched 2026-09-22
     used by The six open read-queue members split three rejected and three earning entries - and the flattest dependency in the set, ASB7, turns out to be a negative regulator of H3K9me3 via SUV39H1 degradation
264. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
     UniProtKB entry Q9H672 (ASB7_HUMAN), cc_function and cc_subcellular_location read verbatim with evidence codes; fetched 2026-09-22 by exact-gene query returning exactly one reviewed record
     used by The six open read-queue members split three rejected and three earning entries - and the flattest dependency in the set, ASB7, turns out to be a negative regulator of H3K9me3 via SUV39H1 degradation
265. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     UniProtKB entry O95985 (TOP3B_HUMAN), retrieved by gene_exact:TOP3B AND organism_id:9606 AND reviewed:true with fields accession, id, protein_name, gene_names, length, cc_subcellular_location, ft_domain, cc_function, fetched 2026-09-22 (exactly one reviewed result)
     used by TOP3B (O95985) - the only human topoisomerase that works on RNA as well as DNA, delivered to the MYC promoter by an arginine mark, and it has poisons
266. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.analysis
     Analysis staleness report, run 2026-09-22: scripts/check-analysis-staleness.py, classifying each analysis directory as self-measuring by reading its scripts, then diffing the node-file count at the commit that last wrote results.json against HEAD via git ls-tree.
     used by Twenty-five of thirty-six analyses that measure this graph were computed against a graph that no longer exists, and seven stamp a date that never moves
267. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.analysis
     Polarity-versus-MBM discrimination table, run 2026-09-21: analyses/polarity-versus-mbm-discrimination/run.py. 11 lesions scored on KMT2A polarity, MBM in cis and MBM in trans, with each structural call written out in the script and attributed to the graph entry whose breakpoint record it was read from.
     used by Two hypotheses in this graph make the same prediction on every lesion that exists, and the experiment queued to test them picks the one arm where neither speaks
268. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.
     Live graph node files (2,894 ids) and analyses/ledger-staleness-audit/results.json, re-derived 2026-09-24; NCBI Gene exact-symbol resolution of all 15 symbols, 0 fetch failures
     used by WITHDRAWN - "thirteen genuinely absent" was wrong: 14 of the 15 are adjudicated in corpus prose and the fifteenth is not an interactor. Superseded by ana-zero-of-fifteen-again-the-same-worklist-the-same-thirteen-and-the-third-recurrence
269. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.
     analyses/q148-what-the-hoxa-negative-blast-occupies/results148_controls.json C3/C4/C8, re-derived by the coordinator from C:/Temp/q147part/promoter_matrix.tsv
     used by WITHDRAWN: I identified the promoter-matrix column mean as library coverage and called A73051 depth-confounded; the column mean is the enrichment fraction, A73051 is at the 37th-39th percentile of true depth, and the share-versus-depth correlation is negative
270. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.
     scripts/is-symbol-covered.py run on all 15 symbols against 2,895 node files (HGNC rows 45,083; retired/alias index 58,536), plus direct reads of the four adjudicating entries, 2026-09-24
     used by Zero of fifteen, again: the same worklist, the same wrong intermediate answer of thirteen, and the third recurrence of a gap list that cannot see a decision