Oncofusion

start / graph / ana-the-founding-acetylome-that-discovered-the-kmt2a-site-was-run-in-a-panel-containing-mv4-11-a-kmt2a-aff1-line

Analysismoderate confidence 3 of 5: One strong study, or several smaller consistent ones.q165-the-retained-acetylation-site

The 2015 paper did not discover the KMT2A acetylation site - it inherited it from the 2009 Choudhary acetylome, which was run in a cell panel that includes MV4-11, a KMT2A::AFF1 line

also called Choudhary 2009 KMT2A acetylation · where K1130 came from

The famous clock paper did not find the chemical tag on MLL1 itself - it looked the positions up in a 2009 survey that catalogued acetylation across thousands of proteins. That 2009 survey was done partly in MV4-11, a leukaemia cell line that carries the exact fusion this project studies. So the tag may already have been seen in the right kind of cell, six years before anyone connected it to the clock, and sixteen years before anyone asked about the fusion.

The same thing, for a scientist

PMID 25751424 states plainly that its four KMT2A lysines came from a prior global acetylome [ref 35 = Choudhary et al., Science 2009, PMID 19608861], not from MS performed in that study. Three independent peer-reviewed sources describe the Choudhary acetylome as having been performed in (among others) MV4-11, a t(4;11) KMT2A::AFF1 AML line. This does NOT establish that the KMT2A peptides came from MV4-11 rather than from A549 or Jurkat, and the Science supplementary table that would settle it is paywalled (HTTP 403). But it moves the question from 'nobody has looked' to 'the data that would answer this may already have been acquired', which is a different and much cheaper problem.

Go deeper
The provenance chain, stated by the paper itself

"While MLL1 acetylation has not been studied previously, mass spectrometry (MS) profiling for global protein acetylome identified four lysine residues as acetylated in MLL1 [35]. These are K636, K1130, K1133 and K1235 in the human isoform of MLL1 [35]." 1

Reference 35 resolves, in the paper's own bibliography, to:

Choudhary C. et al. Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 2009;325:834-40. PMID 19608861, DOI 10.1126/science.1175371 12

So the discovery claim for these four sites belongs to a 2009 proteomics paper, not to the 2015 circadian paper. The 2015 paper's contribution at the site level is validation (a site-specific antibody, K→R mutants of a fragment) and the SIRT1 connection - not site mapping.

This matters for citation practice in this graph: a beat that cites 25751424 for "KMT2A is acetylated at K1130" is citing the wrong paper for the primary observation. 25751424 is the right citation for "SIRT1 deacetylates KMT2A at K1130/K1133 in a circadian manner".

What cell lines the 2009 acetylome used, and why one of them is the point

The Science paper is not in PMC and science.org returns HTTP 403 to both the article and the supplementary download, so this graph has not read it directly 5. Three independent peer-reviewed papers that did read it describe its cell material 3:

sourcewhat it says
Understanding the acetylome (PMC4216940, 2014)"acetylation-based immunoprecipitation to enrich acetylated peptides from MV4-11 cells (a human acute myeloid leukemia cell line), followed by high-resolution MS, Choudhary et al. identified ~1,000 protein acetylation sites"
The cardiac acetyl-lysine proteome (PMC3699649, 2013)lists the comparison acetylomes as mouse liver, "human acute myeloid leukemia cell line, MV4-11 [3]" (ref 3 = Choudhary), and human liver
Is acetylation a metabolic rheostat… (PMC4400303, 2015)"Lys 1088 in IGF1R was acetylated in a human myeloid leukemia cell line, MV4-11 (Choudhary et al., 2009)"

A fourth (PMC4905271, 2015) lists the human lines behind PhosphoSitePlus acetylation calls as "A549 (pulmonary), HeLa (cervical), Jurkat (T lymphocyte), K562 (erythroid) and/or MV4-11", i.e. MV4-11 is one of a panel, not the only line.

MV4-11 is CVCL_0064, karyotype 48,XY,t(4;11)(q21;q23),+8,+19, carrying the gene fusion KMT2A-AFF1 plus a FLT3-ITD 4. It is this graph's index fusion in a cell line.

🔴 The two limits that stop this being the headline it looks like

Limit 1 - which line contributed the KMT2A peptide is NOT established. Choudhary used a panel. The four KMT2A sites could have come entirely from A549 or Jurkat. Settling this needs one lookup of Q03164 in the Science Supplementary Tables, which are behind a 403. This is the single cheapest open action in this beat, and anyone with institutional access to Science can close it in five minutes.

Limit 2 - and this one does not go away even if the peptide did come from MV4-11. K1130/K1133 sit at residues 1126-1137, which is shared sequence: MV4-11 expresses a wild-type KMT2A allele and a KMT2A::AFF1 allele, and the tryptic peptide APPIKPIKPVTR is identical in both proteins. A bottom-up MS hit on that peptide therefore cannot distinguish the fusion protein from wild-type KMT2A. The strongest statement the experiment could ever support is "this site is acetylated in a KMT2A::AFF1 cell" - never "the fusion protein is acetylated".

This is the same failure mode this graph has recorded before under a different name: two true facts joined is not a verified fact. The deposit used MV4-11 and the deposit found acetyl-K1130 would not licence the fusion is acetylated at K1130. Distinguishing them requires an approach that resolves the two proteins - a fusion-junction peptide in the same run, immunoprecipitation of the fusion, or top-down/middle-down MS.

What this does change

absence-q168-no-primary-study-among-the-ninety-citing-the-kmt2a-k1130-acetylation-site-has-asked-about-the-fusion is correct and stands: no primary study has asked. But the framing that follows from it - the experiment has never been done - needs softening to the experiment has never been asked, and the raw material for part of it may already exist. Those are different states of the world and they imply different next steps: the first implies wet work, the second implies a database lookup and possibly a re-analysis of deposited spectra.

Facts and figures
scriptcomputed inline (Europe PMC + Cellosaurus + science.org probe), 2026-09-24
statusrun
methodRead ref 35 out of PMC4732879's bibliography; resolved it to PMID 19608861 via Europe PMC; searched Europe PMC full text for BODY:"Choudhary" AND BODY:"MV4-11" and read the matching passages; queried Cellosaurus for MV4-11; probed science.org for the article and supplementary.
result summaryThe site discovery belongs to Choudhary 2009, not to Aguilar-Arnal 2015. Choudhary's panel includes MV4-11 (KMT2A::AFF1). Which line contributed the KMT2A peptides is NOT established and needs the paywalled supplementary table.
discovery paper pmid19608861
validation paper pmid25751424
cell lineMV4-11
cellosaurusCVCL_0064
cell line fusionKMT2A-AFF1
cell line lineagemyeloid / biphenotypic monocytic, NOT B-lymphoid
peptide can distinguish fusion from wildtypefalse
peptideAPPIKPIKPVTR
peptide coordinatesQ03164 1126-1137, shared by wild-type KMT2A and KMT2A::AFF1
blocking stepChoudhary 2009 Supplementary Table S1-S3 lookup for Q03164 - science.org 403
relationship to existing entriesDoes not duplicate absence-q168-...; that entry bounds who has WRITTEN about the site in a fusion context. This entry is about where the site came from and what material was already in the instrument. It softens, but does not refute, that entry's framing.
inputs
[
  "PMC4732879 fullTextXML",
  "Europe PMC EXT_ID:19608861 core record",
  "Europe PMC full-text search BODY:\"Choudhary\" AND BODY:\"MV4-11\" AND BODY:\"lysine acetylation\" (10 hits)",
  "Cellosaurus CVCL_0064",
  "science.org HTTP probe (403)"
]
sites inherited
[
  "K636",
  "K1130",
  "K1133",
  "K1235"
]
measurements
[
  {
    "quantity": "secondary sources naming MV4-11 as Choudhary 2009 material",
    "subject": "Europe PMC BODY:\"Choudhary\" AND BODY:\"MV4-11\" AND BODY:\"lysine acetylation\"",
    "value": 3,
    "units": "papers",
    "n": 10,
    "universe": "10 full-text hits returned by that query, read by hand",
    "null": null,
    "note": "3 of 10 hits carried an explicit attribution sentence; the other 7 name MV4-11 for unrelated reasons. No PRIMARY source was readable."
  },
  {
    "quantity": "sources establishing which cell line produced the KMT2A peptides",
    "subject": "Choudhary 2009 per-site provenance for Q03164",
    "value": 0,
    "units": "sources",
    "n": 0,
    "universe": "everything readable without a Science subscription",
    "null": null,
    "note": "a zero that is an access failure, not an absence"
  }
]
How this could bite us back
  • MV4-11 is a myeloid, FLT3-ITD line. Evidence imported from it into the B-lymphoid infant-ALL index disease crosses both a lineage boundary and a co-mutation boundary that this graph documents as material elsewhere; a result in MV4-11 is not a result in SEM or RS4;11.
  • If the site is found acetylated in MV4-11 and an intervention is built on it, the intervention would be acting on wild-type KMT2A in every cell in the body as well, because the site is in shared sequence. There is no fusion-specific surface here - by construction, since the whole point of the site is that it is retained.
Still open
  1. Open Choudhary 2009 Supplementary Tables S1-S3 and look up Q03164. If the KMT2A acetyl peptides are annotated to MV4-11, the site has been observed in a KMT2A::AFF1 cell since 2009 and nobody in sixteen years has said so. This is one lookup behind a paywall and is the highest value-per-minute action in this beat.
  2. Are the deposited spectra from Choudhary 2009 still retrievable anywhere (Tranche, PRIDE mirror, a re-analysis deposit)? If so, the fusion-junction peptide question could be asked of the original data rather than requiring new material.
  3. Does any KMT2A::AFF1 cell line proteomics deposit contain a fusion-junction tryptic peptide at all? Without one, no bottom-up experiment in these cells can attribute a shared-region modification to the fusion rather than to the wild-type allele, and that is a design constraint on every experiment this beat might propose.
Every source behind this entry (5)
  1. E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper

    PMID 25751424 attributes the identification of the four acetylated KMT2A lysines to a prior global acetylome study, its reference 35, which its bibliography gives as Choudhary et al., Science 2009;325:834-40.

    NAD(+)-SIRT1 control of H3K4 trimethylation through circadian deacetylation of MLL1 · Aguilar-Arnal L, Katada S, Orozco-Solis R, Sassone-Corsi P · Nature Structural & Molecular Biology 22(4):312-8 2015
    PMID 25751424DOI
    What this evidence cannot show

    The reference-list entry was read from the same Europe PMC XML as the sentence; the reference numbering and the bibliography were cross-checked (ref 35 = Choudhary, Science 2009, PMID 19608861 present in the record). Per this project's rule on reference-list identifier harvesting, the PMID was taken from the bibliography entry that carries Choudhary's title, not from a global regex over the file.

    Evidence that argues against this (1)
    • A paper's attribution of prior discovery is its authors' reading of the literature, not a priority determination. If an earlier low-throughput report of KMT2A acetylation exists that Aguilar-Arnal et al. did not cite, the provenance chain in this entry is wrong at its first link - and the paper's own words, 'MLL1 acetylation has not been studied previously', are precisely the kind of claim that is routinely falsified by an older paper. No search for one was run. Separately, reference numbering in an NIHMS author manuscript can differ from the version of record; ref 35 was matched to Choudhary by title, which protects against that.
  2. E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper

    Choudhary et al., Science 2009, reports 3,600 lysine acetylation sites on 1,750 proteins identified by high-resolution mass spectrometry, with quantitation under SAHA and MS-275.

    Lysine acetylation targets protein complexes and co-regulates major cellular functions · Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M · Science 325(5942):834-40 2009
    PMID 19608861DOI
    What this evidence cannot show

    ABSTRACT ONLY. The full text is not in PMC and science.org returns 403 to this agent, so the Methods, the cell panel and the per-site supplementary tables were NOT read. Every statement here about which cells were used comes from secondary sources [E3], not from this paper.

    Evidence that argues against this (1)
    • This abstract does not say whether KMT2A was among the 1,750 proteins, so it cannot by itself support anything about the KMT2A sites. Worse, there is an unresolved inconsistency inside this entry's own evidence: the abstract reports 3,600 sites on 1,750 proteins, while the secondary source quoted in [E3] (PMC4216940) says Choudhary et al. identified '~1,000 protein acetylation sites' from MV4-11 cells. Those two numbers cannot both describe the same experiment. The most likely reconciliation is that the MV4-11 arm contributed a subset - which, if true, makes it LESS likely that any given KMT2A site came from MV4-11, and cuts directly against this entry's point. It is unresolved because the full text is behind a 403.
  3. E3moderate confidence 3 of 5: One strong study, or several smaller consistent ones.review

    Three independent peer-reviewed papers describe the Choudhary 2009 acetylome as having been performed in MV4-11, a human acute myeloid leukaemia cell line; a fourth lists MV4-11 as one of a panel including A549, HeLa, Jurkat and K562.

    Understanding the acetylome: translating targeted proteomics into meaningful physiology · Kim SC, et al. (as cited); primary quotation from Am J Physiol Endocrinol Metab review · American Journal of Physiology - Cell/Endocrinology review, PMC4216940 2014
    PMID 25186010
    What this evidence cannot show

    ALL FOUR SOURCES ARE SECONDARY. None is the Choudhary paper. They agree with each other, which is reassuring but not independent in the strong sense - reviews copy cell-line attributions from each other. More importantly, NONE of them says which cell line the KMT2A peptides specifically came from; they describe the study's material, not the provenance of any individual site. The corroborating sources are PMC3699649 (PMID 23755013 region, cardiac acetyl-lysine proteome), PMC4400303 (PMID 25901320 region) and PMC4905271; their PMIDs were not each separately resolved, so only the first is carried as the formal citation here and the others are quoted in the body as read from Europe PMC full text.

    Evidence that argues against this (1)
    • If the KMT2A peptides came from A549 or Jurkat rather than MV4-11, the leukaemia connection in this entry evaporates entirely and only the provenance correction (the site is Choudhary's, not Aguilar-Arnal's) survives. That is a live possibility and nothing here excludes it.
  4. E4established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

    MV4-11 (Cellosaurus CVCL_0064) has karyotype 48,XY,t(4;11)(q21;q23),+8,+19 and carries the KMT2A-AFF1 gene fusion together with a FLT3 internal tandem duplication.

    Cellosaurus CVCL_0064 (MV4-11) · Cellosaurus, SIB 2026
    What this evidence cannot show

    Cellosaurus records the ATCC karyotype (CRL-9591). MV4-11 is annotated in Cellosaurus under 'childhood acute monocytic leukemia' - it is a myeloid/biphenotypic line, NOT the B-lymphoid infant-ALL phenotype that is this graph's index disease, even though the fusion is the same. Any inference from MV4-11 to infant B-ALL crosses a lineage boundary this graph repeatedly records as load-bearing.

    Evidence that argues against this (1)
    • Cellosaurus aggregates depositor-supplied karyotypes rather than verifying them, and leukaemia line stocks drift and are misidentified often enough that this is not a formality. The karyotype here is corroborated across ATCC, so the fusion call is safe; the softer link is what it does NOT say. It gives no breakpoint, no transcript and no isoform, so it cannot establish that MV4-11's fusion retains residue 1130 - that comes from the exon map, not from here. And MV4-11 is annotated as childhood acute MONOCYTIC leukaemia: it shares the fusion with the index disease and not the lineage.
  5. E5established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

    The Science article and its supplementary tables for DOI 10.1126/science.1175371 return HTTP 403 to this agent, so the per-site cell-line provenance could not be read.

    What this evidence cannot show

    A 403 is an access failure at this agent's IP, not a statement that the material is unavailable. Anyone with institutional access almost certainly can open it. Recorded so the gap is attributable to the instrument and not mistaken for an absence in the literature - this project has previously mis-filed a tool failure as a fact about the world.

    Evidence that argues against this (1)
    • The supplementary URL was CONSTRUCTED from a guessed filename pattern, so its 403 may be a wrong-URL error rather than a paywall - a distinction this entry cannot make and should not paper over. The article-level 403 is real. Either way a 403 at this host says nothing about the content, and the natural counter-evidence is trivial: anyone with a Science subscription opening Table S1 would either confirm or destroy this entry's central suggestion in one lookup.
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