Oncofusion

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Analysisstrong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.q165-the-retained-acetylation-site

The blind spot is closed: all four K1130-and-leukaemia full-text hits are reviews restating the source paper, and the citation-network bound survives 26 nomenclatures rather than five

also called K1130 leukemia four hits · citation network bound 26 terms

Only four papers in the open literature mention both this exact protein spot and the word leukaemia, and all four are review articles that simply repeat the original finding rather than testing anything. Re-running the search with 26 different ways of writing 'leukaemia fusion' instead of five still finds nobody who has done the experiment.

The same thing, for a scientist

Two gaps in the previous bound are closed. (1) The four Europe PMC full-text hits for BODY:"K1130" AND BODY:"leukemia" had not been read; all four are reviews (PMC13142947, PMC10641101, PMC4482757, PMC6521413) and the three readable ones restate PMID 25751424 verbatim without any new measurement, any fusion context or any leukaemia experiment. (2) The citation-network bound was built on five nomenclatures; it was re-run with 26. Nothing changes the conclusion, and the added terms surfaced one paper the five-term bound missed - PMID 33328229, a genuine primary research article - which turns out to use Hoxa9 as a non-circadian control gene in MEFs and contains no leukaemia content at all.

Go deeper
🟢 The four hits, read
PMCID / PMIDvenue, yeartypewhat it says about K1130
PMC13142947 / 41994991Biochem J 2026review"Mass profiling and mutagenesis studies suggest that K1130 and K1133 within MLL are the target sites of SIRT1" - a restatement, in a section contrasting SIRT1's opposite effect on SUV39H1 K266
PMC10641101 / 37953273Signal Transduct Target Ther 2023review"acetylation of MLL1 at two conserved residues, K1130 and K1133, by sirtuin1 (SIRT1) affects its methyltransferase activity" - one sentence in a list of co-activator PTMs. ⚠️ It also misattributes the writer: SIRT1 is the ERASER, not the acetyltransferase.
PMC6521413 / 31092281Clin Epigenetics 2019review"MLL1 circadian enzymatic activity appears to be directed by posttranslational modifications consisting of rhythmic acetylation at K1130 and K1133" - restatement, correctly attributing the mouse systems
PMC4482757 / 26049753Curr Opin Hematol 2015review✅ RECORD RESOLVED cycle 158 via PubMed (Europe PMC still 500s). Li L & Bhatia R, Curr Opin Hematol 2015;22(4):324-9, doi 10.1097/MOH.0000000000000152. PubMed article_types includes Review, confirming the classification this table had already assigned it. Abstract and MeSH carry no KMT2A, MLL or 11q23 term - the leukaemia MeSH are Leukemia, Myelogenous, Chronic, BCR-ABL Positive and Leukemia, Myeloid, Acute, with Sirtuin 1 and fms-Like Tyrosine Kinase 3. Full text still not retrieved, so a K1130 mention in its body remains possible - but a review cannot be the primary report this bound is looking for, so the article type settles the question the bound asks.

Three of four read in full and the fourth resolved at the record level; none contains a measurement; none mentions a KMT2A fusion; none asks the question. All four are confirmed reviews by PubMed article type. 1

🔵 The fourth was the one that would have mattered most, and it is now resolved at the record level - a Current Opinion in Hematology review of SIRT1 in leukaemia stem cells, by Li and Bhatia (authorship confirmed against PubMed cycle 158), the group behind the SIRT1/FLT3-ITD AML work. Its MeSH assign it to CML and FLT3-ITD AML with no KMT2A term. If any review was going to connect MLL1 acetylation to leukaemia, it is that one. It is unread because of a server error, not because of an absence, and that distinction is recorded rather than glossed.

🟠 The search term itself is contaminated, and this is the reusable finding

BODY:"leukemia" is not a leukaemia-biology filter for this protein. KMT2A's own name expands to Mixed-Lineage Leukemia 1 / mixed lineage leukemia 1, so every paper that spells out MLL1 once matches the term. Verified in the retrieved text:

  • PMC13142947: "the histone methyltransferase Mixed-Lineage Leukemia 1 (MLL1)"
  • PMC6521413: "the histone methyltransferase mixed lineage leukemia 1 (MLL1)"

So the four hits are four papers that named MLL1 in full, not four papers about leukaemia. The filter did almost no work. This belongs in data/symbol-collisions.json as a general rule: for any gene whose expanded name contains a disease word — KMT2A/MLL (leukemia), PML (promyelocytic leukemia), AML1/RUNX1 (acute myeloid leukemia), CML-associated names — the disease word cannot be used as a topic filter, because the gene name supplies it. That is a whole class, not one token.

🟢 26 nomenclatures over the 90-paper citation network

The prior bound used five terms. Twenty-six were run, each as a quoted BODY phrase over CITES:25751424_MED (n = 90). Full list and per-term PMIDs in analyses/q165-the-retained-acetylation-site/citation-network-nomenclature-bound.json 2.

termhitstermhits
MLL-AF0menin0
MLL::AF0MEN10
MLL1 fusion0t(4;11)0
MLL fusion0t(9;11)0
KMT2A fusion011q231
KMT2A-rearranged0revumenib0
KMT2A rearranged0leukemogenesis0
MLL-rearranged2infant leukemia0
MLL rearranged2acute lymphoblastic leukemia1
AFF11acute myeloid leukemia7
AF41DOT1L3
MLLT31HOXA93
AF92translocation19

Union of every leukaemia-specific term: five papers — 41994991, 26335311, 37953273, 33328229, 26049753. Four are reviews.

The fifth is a primary paper the five-term bound missed, surfaced only by HOXA9: PMID 33328229, Greco et al., Sci Adv 2020, S-adenosyl-l-homocysteine hydrolase links methionine metabolism to the circadian clock and chromatin remodeling. Read in full: it contains zero occurrences of HOXA9 in upper case — the hit is mouse Hoxa9, used as "the MLL1-controlled gene Hoxa9" in a negative control showing H3K4me3 there does NOT change under AHCY inhibition. Its single leukemia match is HL-60 in a reference title. It is a circadian-metabolism paper and it does not touch the fusion 3.

🟡 The bound stands and is now much stronger — but note what nearly happened. A five-term list described the citing set as "all three are reviews". With HOXA9 added the set contains a primary research article. The conclusion did not change; the sentence would have had to. This is the third time this project has recorded that a single nomenclature is not a bound, and the first time the extra term surfaced a non-review.

What the bound now says, precisely

Of 90 papers citing PMID 25751424, and across 26 nomenclatures spanning fusion names, partner genes, cytogenetics, disease names, the menin axis and the drug class:

  • zero mention menin, MEN1, t(4;11), t(9;11), revumenib, leukemogenesis, infant leukemia, or any KMT2A-prefixed fusion nomenclature;
  • five contain any leukaemia-specific term at all, of which four are reviews and the fifth is a circadian-metabolism primary paper whose only touchpoint is a mouse Hoxa9 negative control;
  • no primary study, under any nomenclature tested, has asked whether a KMT2A fusion is acetylated at K1130/K1133 or what that would do.
Facts and figures
scriptanalyses/q165-the-retained-acetylation-site/citation-network-nomenclature-bound.json (persisted query set)
statusrun
result summaryAll four K1130+leukaemia hits are reviews; three read and none contains a measurement. 26-term citation-network bound holds: zero for menin, MEN1, t(4;11), t(9;11), revumenib, leukemogenesis, infant leukemia and all KMT2A-prefixed fusion names. The one primary paper the wider term list surfaced is a circadian-metabolism study using Hoxa9 as a negative control.
citing set size90
nomenclatures tested26
nomenclatures returning zero14
of which reviews4
of which primary1
primary paper verdictPMID 33328229 - circadian metabolism, Hoxa9 as a negative control, no fusion content
search term contaminationBODY:"leukemia" is satisfied by KMT2A's own expanded name (Mixed-Lineage Leukemia 1). Verified verbatim in PMC13142947 and PMC6521413. The filter did almost no topical work.
absence classliterature-absence-bounded
absence class basisAll four Europe PMC full-text hits are reviews; the three readable ones restate PMID 25751424 without new measurement.
measurements
primary research articles…1.000primary research articles among the leukaemia-term hits: 1full-text hits for the re…3.000full-text hits for the residue and the disease word, read: 3nomenclatures returning z…14.0nomenclatures returning zero over the citing set: 14
inputs
[
  "Europe PMC BODY:\"K1130\" AND BODY:\"leukemia\" (4 hits, all retrieved as metadata; 3 of 4 full texts read)",
  "Europe PMC CITES:25751424_MED (90 papers) x 26 quoted BODY terms"
]
leukaemia term union pmids
[
  "41994991",
  "26335311",
  "37953273",
  "33328229",
  "26049753"
]
unread hit
{
  "pmid": "26049753",
  "pmcid": "PMC4482757",
  "reason": "Europe PMC fullTextXML returns HTTP 500",
  "why_it_matters": "it is a review of SIRT1 in leukaemia stem cells by the group behind the SIRT1/FLT3-ITD AML work - the most topically relevant of the four"
}
measurements — the numbers behind the chart
[
  {
    "quantity": "nomenclatures returning zero over the citing set",
    "subject": "CITES:25751424_MED AND BODY:<term>",
    "value": 14,
    "units": "terms",
    "n": 26,
    "universe": "26 quoted BODY terms spanning fusion names, partner genes, cytogenetics, diseases, menin axis and drugs",
    "null": null,
    "note": "including every KMT2A-prefixed nomenclature, menin, MEN1, both translocations, revumenib and leukemogenesis"
  },
  {
    "quantity": "primary research articles among the leukaemia-term hits",
    "subject": "union of leukaemia-specific terms over the 90 citing papers",
    "value": 1,
    "units": "papers",
    "n": 5,
    "universe": "5 papers matched by any leukaemia-specific term",
    "null": null,
    "note": "and that one contains no leukaemia content - it was surfaced by a mouse gene symbol used as a negative control. The prior five-term bound reported 'all three are reviews'; with 26 terms the correct sentence is 'four of five are reviews and the fifth is not about leukaemia'."
  },
  {
    "quantity": "full-text hits for the residue and the disease word, read",
    "subject": "BODY:\"K1130\" AND BODY:\"leukemia\"",
    "value": 3,
    "units": "papers",
    "n": 4,
    "universe": "the complete Europe PMC hit set",
    "null": null,
    "note": "the fourth is blocked by an HTTP 500, not by an absence"
  }
]
How this could bite us back
  • A strengthened absence is an invitation to do the experiment, and the experiment here has no obvious readout: the site is in shared sequence, so 'is the fusion acetylated at K1130' cannot be answered by any bottom-up proteomics on a fusion-bearing cell without a fusion-resolving step. A well-bounded absence with no tractable experiment behind it can absorb a lot of effort.
Still open
  1. What does PMID 26049753 (Li & Bhatia, Curr Opin Hematol 2015) say about K1130? It is the one unread hit and the most topically relevant, and Europe PMC's server error is the only thing in the way.
  2. Should a disease-word-in-gene-name collision class be added to data/symbol-collisions.json? KMT2A/MLL supplies 'leukemia', PML supplies 'promyelocytic leukemia', RUNX1/AML1 supplies 'acute myeloid leukemia'. Any bounded absence in this project that filters on a disease word while querying one of these genes is measuring nothing.
  3. Does the full-text route miss measurements that live only in supplementary tables? This project already records that a PubMed zero is bounded by abstracts; a Europe PMC BODY zero is bounded by indexed full text, which for most publishers excludes supplementary files - and a residue-level acetylation measurement is exactly the kind of thing that appears only in a supplementary table.
Every source behind this entry (3)
  1. E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database

    All four Europe PMC full-text hits for BODY:"K1130" AND BODY:"leukemia" are review articles; the three whose full text is retrievable restate PMID 25751424 without any new measurement, and one of them (PMC10641101) misdescribes SIRT1 as the acetyltransferase rather than the deacetylase.

    What this evidence cannot show

    THREE of four were read. PMC4482757 (PMID 26049753, Li & Bhatia, Curr Opin Hematol 2015, 'Role of SIRT1 in the growth and regulation of normal hematopoietic and leukemia stem cells') returned HTTP 500 from Europe PMC's fullTextXML endpoint on repeated attempts and was NOT read. Its abstract does not mention MLL1 acetylation, so whatever it says about K1130 is in its body and is unknown. It is a review, so it cannot contain a primary experiment - but it could contain an interpretation connecting this site to leukaemia that nothing else does, and that possibility is open.

    Evidence that argues against this (1)
    • The one unread paper is the most topically relevant of the four. A bound with a named, addressable hole is honest, but it is still a hole, and anyone with access to Current Opinion in Hematology 2015;22(4) can close it in one minute.
  2. E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.dataset

    Across 26 quoted BODY nomenclatures over the 90 papers citing PMID 25751424, menin, MEN1, t(4;11), t(9;11), revumenib, leukemogenesis, infant leukemia and every KMT2A-prefixed fusion nomenclature return zero.

    What this evidence cannot show

    Europe PMC does not return a querytranslation field, so the rule-94/95 discipline of reading back the executed query cannot be applied directly; instead every term was sent as a quoted BODY phrase (so the rule-95 unquoted-cytogenetic-term failure cannot fire) and the exact query string is persisted beside each count. CITES coverage is limited to citations Europe PMC has resolved, which is incomplete for older and non-OA venues - the true citing set is larger than 90 and the terms were only run against the 90.

    Evidence that argues against this (1)
    • A bound over a citation network cannot see a paper that studied this site without citing the source. The full-text route (BODY:"K1130") is the complement to that and returns 25 papers across all of Europe PMC, of which only 4 touch leukaemia at all - but full-text indexing also has coverage gaps, particularly for supplementary material and figures, where a residue-level measurement is most likely to live.
  3. E3established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper

    PMID 33328229 (Greco et al., Science Advances 2020) is a primary research article in the citing set whose only leukaemia-adjacent content is the use of mouse Hoxa9 as an MLL1-controlled negative-control gene in MEFs; it contains no uppercase HOXA9, no fusion content, and its single 'leukemia' match is HL-60 in a reference title.

    S-adenosyl-l-homocysteine hydrolase links methionine metabolism to the circadian clock and chromatin remodeling · Greco CM, Cervantes M, Fustin JM, Ito K, Ceglia N, Samad M, Shi J, Koronowski KB, et al. · Science Advances 2020
    PMID 33328229
    What this evidence cannot show

    Read via full-text XML text extraction and token search, not by reading the whole paper. The judgement that the Hoxa9 usage is a negative control comes from the sentence 'H3K4me3 and expression levels of the MLL1-controlled gene Hoxa9 displayed no significant change upon AHCY inhibition (fig. S7, D and E)'; supplementary figure S7 itself was not seen.

    Evidence that argues against this (1)
    • The 'negative control' reading rests on one sentence and on Supplementary Fig S7, which was NOT seen - Europe PMC full-text XML does not carry supplementary figures. If S7 shows Hoxa9 H3K4me3 behaving in some interesting way, the paper is doing more with an MLL1 target locus than this entry credits, and the claim that the citing set contains no leukaemia-relevant primary work weakens. The screen was also a token search, not a read: a discussion of MLL1 in leukaemia phrased without any of the 26 terms would have been missed by both instruments.
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