CSPG4 / NG2 - the flow-cytometry surrogate for a broken KMT2A, and a direct target gene of the fusion that makes it

[
  {
    "cohort": "313 adult ALL, MLL status in 120 B-precursor",
    "sensitivity": 0.89,
    "specificity": 0.89,
    "ppv": 0.93,
    "pmid": "12886247",
    "title": "Expression of the human homologue of rat NG2 in adult acute lymphoblastic leukemia: close association with MLL rearrangement and a CD10(-)/CD24(-)/CD65s(+)/CD15(+) B-cell phenotype.",
    "authors": "Schwartz S, Rieder H, Schläger B, et al.",
    "venue": "Leukemia",
    "year": 2003,
    "title_provenance": "Title/authors/venue backfilled from PubMed esummary on 2026-09-20 because this citation stored a bare PMID with no title, which made it unscoreable by verify-citations.py. BACKFILLING IS NOT VERIFICATION: it confirms the PMID resolves to a real paper, not that this is the right paper for the claim. That still requires reading."
  },
  {
    "cohort": "533 acute leukaemias, 20% cut-off",
    "sensitivity_within_mll_r": 0.81,
    "note": "11 adult AML 7.1-positive but MLL-germline",
    "pmid": "10914547",
    "title": "Detection of acute leukemia cells with mixed lineage leukemia (MLL) gene rearrangements by flow cytometry using monoclonal antibody 7.1.",
    "authors": "Wuchter C, Harbott J, Schoch C, et al.",
    "venue": "Leukemia",
    "year": 2000,
    "title_provenance": "Title/authors/venue backfilled from PubMed esummary on 2026-09-20 because this citation stored a bare PMID with no title, which made it unscoreable by verify-citations.py. BACKFILLING IS NOT VERIFICATION: it confirms the PMID resolves to a real paper, not that this is the right paper for the claim. That still requires reading."
  },
  {
    "cohort": "1382 B-ALL, NG2 above 10%",
    "ppv": 0.966,
    "note": "85/88 NG2-positive carried KMT2A-r",
    "pmid": "38468826",
    "title": "NG2 Molecule Expression in Acute Lymphoblastic Leukemia B Cells: A Flow-Cytometric Marker for the Rapid Identification of KMT2A Gene Rearrangements.",
    "authors": "Bisegna ML, Peragine N, Elia L, et al.",
    "venue": "Mediterr J Hematol Infect Dis",
    "year": 2024,
    "title_provenance": "Title/authors/venue backfilled from PubMed esummary on 2026-09-20 because this citation stored a bare PMID with no title, which made it unscoreable by verify-citations.py. BACKFILLING IS NOT VERIFICATION: it confirms the PMID resolves to a real paper, not that this is the right paper for the claim. That still requires reading."
  },
  {
    "cohort": "104 consecutive childhood ALL",
    "note": "9/9 NG2-positive had MLL-r; 0/95 NG2-negative had MLL-r",
    "pmid": "8562939",
    "title": "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.",
    "authors": "Behm FG, Smith FO, Raimondi SC, et al.",
    "venue": "Blood",
    "year": 1996,
    "title_provenance": "Title/authors/venue backfilled from PubMed esummary on 2026-09-20 because this citation stored a bare PMID with no title, which made it unscoreable by verify-citations.py. BACKFILLING IS NOT VERIFICATION: it confirms the PMID resolves to a real paper, not that this is the right paper for the claim. That still requires reading."
  }
]

{
  "infant_ALL": 7,
  "child_ALL": 12,
  "infant_AML": 28,
  "child_AML": 14,
  "pmid": "33135273",
  "title": "Quantification of NG2-positivity for the precise prediction of KMT2A gene rearrangements in childhood acute leukemia.",
  "authors": "Zerkalenkova E, Mikhaylova E, Lebedeva S, et al.",
  "venue": "Genes Chromosomes Cancer",
  "year": 2021,
  "title_provenance": "Title/authors/venue backfilled from PubMed esummary on 2026-09-20 because this citation stored a bare PMID with no title, which made it unscoreable by verify-citations.py. BACKFILLING IS NOT VERIFICATION: it confirms the PMID resolves to a real paper, not that this is the right paper for the claim. That still requires reading."
}

{
  "subcellular": "plasma membrane, type I single-pass proteoglycan (Q6UVK1, 2322 aa). This is the one entry in this tranche where the compartment has been read directly in KMT2A-rearranged blasts: NG2 positivity is scored by unpermeabilised diagnostic flow cytometry and is used quantitatively to predict a KMT2A rearrangement, and the KMT2A-r B-ALL functional literature treats it as membrane-bound and acting in cis with ITGA4 in the membrane. A shed, non-membrane pool exists in other systems.",
  "subnuclear": "not applicable - a single-pass plasma membrane proteoglycan; no nuclear pool reported in any source read for this beat",
  "how_shown": "unpermeabilised multiparameter flow cytometry on childhood acute leukaemia blasts, quantified against KMT2A rearrangement status (PMID 33135273, PMID 38468826); membrane-bound designation and ITGA4 co-dependence in KMT2A-r B-ALL models and PDX (PMID 42345361); MLL-AF4 target-gene status (PMID 39093982)",
  "systems": "childhood KMT2A-rearranged B-ALL patient blasts, KMT2A-r B-ALL cell lines and patient-derived xenografts",
  "node": "localization-plasma-membrane-leukaemic-surface-antigens"
}

{
  "chronos_mean_kmt2a_rearranged": -0.0968,
  "chronos_mean_other_leukaemia": -0.141,
  "difference": 0.0443,
  "pan_essentiality_all_lines": -0.1527,
  "selectivity_rank": 14277,
  "rank_denominator": 17728,
  "provenance": "Joined 2026-09-21 from analyses/depmap-kmt2a-selective-scan-full (generated 2026-09-19T10:12:06Z), the project's own genome-wide scan over 11 KMT2A-rearranged and 43 other leukaemia DepMap lines. NOT re-fetched and NOT independent of that scan: every caveat it carries applies here, including that the KMT2A-rearranged arm is a small number of lines drawn from nine individuals, that the rank denominator is 17,728 genes, and that a difference is not a dependency. Added because only 26 of 308 gene entries carried this number, which made any KMT2A-selectivity question answerable for 8% of the corpus.",
  "how_to_read": "A negative difference means MORE required in KMT2A-rearranged lines than in other leukaemia lines. A rank near 17,728 is ANTI-selective. Neither is evidence of a fusion-driven dependency on its own: check pan_essentiality_all_lines before calling anything selective, and note that a paralogue-redundant gene can score near zero for reasons that have nothing to do with this disease - see ana-the-paralogue-redundancy-excuse-is-not-tested-and-my-proxy-decided-the-answer."
}

{
  "claim": "No histone- or DNA-modifying or -reading activity is attributed to CSPG4, and no chromatin mark has ever been measured at the CSPG4 locus in any system, KMT2A-rearranged or otherwise.",
  "date_measured": "2026-09-21",
  "tool": "NCBI esearch db=pubmed (eutils), querytranslation read back from every response; UniProt REST for the architecture",
  "queries": [
    {
      "query": "CSPG4[tiab] AND histone[tiab]",
      "querytranslation": "\"CSPG4\"[Title/Abstract] AND \"histone\"[Title/Abstract]",
      "count": 2,
      "title_checked": "PMID 39523812 (macrophages producing chondroitin sulfate proteoglycan-4 and neuro-cardiac junction impairment in Duchenne muscular dystrophy) and 35127724 (gemcitabine-resistance biomarkers in bladder cancer and the tumour-immune microenvironment). BOTH OFF TOPIC; 0 on topic. Neither reports CSPG4 acting on a histone."
    },
    {
      "query": "CSPG4[tiab] AND epigenetic[tiab]",
      "querytranslation": "\"CSPG4\"[Title/Abstract] AND \"epigenetic\"[Title/Abstract]",
      "count": 2,
      "title_checked": "PMID 42312194 (a neuro-glioma activity-dependent growth review, NLGN3-ADAM10 to AMPA synapses) and 32599896 (NG2/CSPG4 localisation in low- and high-grade gliomas, in which 'genetic and epigenetic alterations were detected' refers to the gliomas' own alterations, not to CSPG4 acting epigenetically). 0 on topic."
    },
    {
      "query": "CSPG4[tiab] AND chromatin[tiab]",
      "querytranslation": "\"CSPG4\"[Title/Abstract] AND \"chromatin\"[Title/Abstract]",
      "count": 2,
      "title_checked": "PMID 33727640 (NG2/CSPG4, CD146/MCAM and VAP1/AOC3 are regulated by myocardin-related transcription factors in smooth muscle cells) and 21079792 (dual DNA methylation patterns in the CNS reveal developmentally poised chromatin and monoallelic expression of critical genes). The SECOND is the closest thing to a locus-level result anywhere in this set - a CNS methylation/poised-chromatin survey in which CSPG4 appears - and it is NOT leukaemia, NOT haematopoietic and not a KMT2A system, so it is recorded here as the one hit worth a future read rather than as support."
    },
    {
      "query": "CSPG4[tiab] AND H3K79[tiab]",
      "querytranslation": "\"CSPG4\"[Title/Abstract] AND \"H3K79\"[Title/Abstract]",
      "count": 0,
      "errorlist_note": "warninglist outputmessages ['No items found.']; quotedphrasesnotfound empty, so both terms are indexed"
    },
    {
      "query": "NG2[tiab] AND H3K79[tiab]",
      "querytranslation": "\"NG2\"[Title/Abstract] AND \"H3K79\"[Title/Abstract]",
      "count": 0,
      "role": "THE ALIAS ARM, and it is the arm that matters, because this entry's own name_collision field records that NG2 is the name the leukaemia literature uses. Zero under both names."
    },
    {
      "query": "NG2[tiab] AND MLL[tiab] AND chromatin[tiab]",
      "querytranslation": "\"NG2\"[Title/Abstract] AND \"MLL\"[Title/Abstract] AND \"chromatin\"[Title/Abstract]",
      "count": 0,
      "role": "the fusion-scoped form under the leukaemia alias, also zero"
    },
    {
      "query": "CSPG4[tiab] AND KMT2A[tiab]",
      "querytranslation": "\"CSPG4\"[Title/Abstract] AND \"KMT2A\"[Title/Abstract]",
      "count": 3,
      "role": "POSITIVE CONTROL through the identical shape: the gene-plus-fusion pairing returns 3 records (PMIDs 42345361, 35734412, 34638301), so the instrument reaches this gene in this disease. It is the MARK clause that empties the query, not the gene or the disease."
    },
    {
      "query": "CSPG4[tiab] AND methylation[tiab]",
      "querytranslation": "\"CSPG4\"[Title/Abstract] AND \"methylation\"[Title/Abstract]",
      "count": 7,
      "role": "breadth control; 7 records, titles not individually read, so not counted as support in either direction. Recorded so a later reader knows the DNA-methylation arm has unread material while the histone arm does not."
    }
  ],
  "aliases_searched": [
    "CSPG4",
    "NG2"
  ],
  "aliases_not_searched": [
    "MCSP",
    "MSK16",
    "HMW-MAA",
    "melanoma chondroitin sulfate proteoglycan",
    "CD-antigen-free forms",
    "7.1 antigen"
  ],
  "absence_class": "not-applicable-as-activity-plus-never-measured-as-locus",
  "absence_class_basis": "Two distinct claims with different standing. The ACTIVITY claim is settled by architecture fetched live, not by a query count, which is what makes it safe (the FLT3 lesson from the previous tranche: a not-applicable asserted from queries alone was wrong). The LOCUS claim is a genuine never-measured bounded by titles and abstracts only, with rule 80 fully in force - an H3K79me2 track at one gene is exactly the supporting panel an abstract index cannot see, and this graph has already been caught by that once, on SET::NUP214 and H3K79 in PMID 18299449 Figure 6A. Four aliases were not searched.",
  "reopening_condition": "The ACTIVITY claim reopens only if a nuclear pool or a chromatin-binding module is reported for CSPG4 - a proteolytic intracellular fragment reaching the nucleus would do it, which is not far-fetched for a shed surface proteoglycan and is worth watching. The LOCUS claim reopens on any H3K79me2, H3K4me3, menin or fusion occupancy track at CSPG4 in a KMT2A-rearranged sample, or any report of CSPG4 surface expression changing under a menin or DOT1L inhibitor. GSE127508 and the published KMT2A::AFF1 occupancy datasets already in this project's queue would answer it without new experiments."
}