Oncofusion

start / graph / ana-unstated-system-yokoyama-menin-unresolved

Analysisestablished confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.Q18b-unstated-systems

Bounded failure: the founding menin-cofactor paper names no fusion, has no PMC record and deposited nothing - and three entries depend on it

also called PMID 16239140 bounded failure · Yokoyama 2005 provenance · menin essential cofactor system

The 2005 paper that established menin as an essential partner for MLL leukaemia never says which fusion proteins it used. It is behind a paywall with no free version anywhere, and it deposited no data, so there is nothing left to ask. Three entries in this graph carry that unknown.

The same thing, for a scientist

Three entries - `ana-menin-dependence-untested-in-septin-and-cytoskeletal-kmt2a-fusions`, `exp-menin-inhibitor-sensitivity-of-kmt2a-septin-fusions` and `hyp-elongation-hijack-is-a-special-case-of-forced-oligomerisation` - each hedge PMID 16239140 with a version of *"the abstract does not state which fusion proteins were used"* [E1]. This beat could not resolve it, and the failure is complete rather than partial: **no full text by any route, and no deposition of any kind**. That matters more here than for any other source in the beat, because this is the paper that put menin in the middle of KMT2A leukaemia biology at all, and the menin interface is this project's central therapeutic hypothesis. The specific question the three entries need - *which fusion partners were tested for menin dependence?* - is the question that decides whether menin dependence is a property of the KMT2A N-terminus (and therefore universal across partners, including the septins) or of particular fusions. A 2005 Cell paper is exactly the vintage at which that question was usually answered with two or three constructs and never tabulated.

Go deeper
Every route tried, and what each returned
RouteResult
PubMed esummary articleidsno pmc identifier
Europe PMC search?query=EXT_ID:16239140&resultType=corepmcid null, isOpenAccess N, inEPMC N
Europe PMC {PMCID}/fullTextXMLnot attempted - no PMCID exists to attempt it with
NCBI efetch db=pmcnot attempted - same reason
elink dbfrom=pubmed&db=gds0 records
esearch db=gds&term=Yokoyama A[Author] AND menin0 records
elink dbfrom=pubmed&db=sra / biosample / bioproject0 records each (a route this beat found uninformative in general)

All run on 2026-09-19 from a single network location. The PMCID absence is decisive in a way an HTTP error is not: the cycle-50 rule requires a PMCID lookup and a fullTextXML fetch to fail, and here the lookup returns no identifier at all, so there is no second fetch to make. Institutional subscription access was not available to this agent and was not attempted - a reader with it would answer this in one minute.

Why no deposition is the expected answer, and why that does not help

A 2005 paper of this design would have generated retroviral transformation assays, colony counts, westerns and targeted ChIP-qPCR. None of those leaves a repository trace even today, and deposition mandates for microarray data were inconsistently enforced then. So the absence here is unsurprising and carries no information about the study's quality.

It does, however, mark a class boundary for this beat's method. The GEO route works on papers whose central experiments are genome-scale. It fails completely on the pre-2010 genetics literature, which is precisely where fusion-partner comparisons were done. This graph's oldest and most load-bearing mechanistic citations are systematically the ones the route cannot reach - and they are systematically the ones whose fusion rosters matter most, because they are the papers that defined which fusions anyone studies.

What is unresolved, and what is not

Coordinator verification, 2026-09-19. This entry's failure is real and it is narrower than 'nobody has read the founding menin paper', which is how it is easy to summarise. Two things come apart:

Unresolved: which MLL fusion proteins were used. The abstract does not name them, the paper has no PMC record at all, and no free route reaches the methods. Every entry hedging on that point is hedging correctly.

Not unresolved: the claim this graph actually leans on. The abstract is 1,341 characters and states it outright — that oncogenic MLL fusion proteins retain an ability to stably associate with menin through a high-affinity, amino-terminal, conserved binding motif and that this interaction is required for the initiation of MLL-mediated leukemogenesis, and that menin is further required for maintenance. The binding-and-requirement claim is therefore sourced at abstract level from the paper that established it, not inherited on trust.

The distinction matters for how far the hedge should travel. What the graph cannot say from this citation is that the requirement was demonstrated in KMT2A::AFF1, or in any named fusion — and given that the partner-provenance audit found 54% of load-bearing experiments come from a non-index fusion, the unnamed fusions here are more likely MLL-AF9 than not. What it can say is that a high-affinity N-terminal menin-binding motif is retained by oncogenic MLL fusions and is required for initiation. Those are different sentences and only the first is blocked.

Facts and figures
scriptnone - Europe PMC core record, NCBI esummary, elink and GEO author search
statusrun
result summaryUnresolved. No PMCID in PubMed or Europe PMC; isOpenAccess N; inEPMC N; zero GEO records by elink or author search; zero SRA/BioSample/BioProject. The paper predates routine deposition for its assay class, so there is no administrative record to interrogate.
what would resolve itInstitutional subscription access to Cell 2005, an interlibrary loan, or a direct request to the authors for the construct list in the Methods. One paragraph closes three graph entries.
resolution classbounded failure
inputs
[
  "PMID 16239140"
]
routes tried
[
  "PubMed esummary articleids (no pmc)",
  "Europe PMC core record (pmcid null, isOpenAccess N, inEPMC N)",
  "elink pubmed->gds (0)",
  "esearch db=gds Yokoyama A[Author] AND menin (0)",
  "elink pubmed->sra, biosample, bioproject (0 each)"
]
entries affected
[
  "ana-menin-dependence-untested-in-septin-and-cytoskeletal-kmt2a-fusions",
  "exp-menin-inhibitor-sensitivity-of-kmt2a-septin-fusions",
  "hyp-elongation-hijack-is-a-special-case-of-forced-oligomerisation"
]
How this could bite us back
  • This graph's central therapeutic hypothesis rests on a founding paper whose experimental roster is unknown to it, so the confidence attached to menin dependence across partners is higher than the readable evidence supports.
  • If menin dependence turns out to have been established in two myeloid fusions only, then extending menin inhibitors to septin-partner and B-lineage disease is an extrapolation the graph has been treating as a fact.
  • An unreadable founding citation cannot be audited, so every downstream entry inherits an error mode that no checker in this toolchain can detect.
Still open
  1. Which MLL fusion proteins were tested for menin dependence in the founding 2005 experiments? This is the single highest-value unreadable sentence in this beat.
  2. Is menin dependence a property of the KMT2A N-terminus alone? If so, the septin and cytoskeletal fusions this graph flags as untested are predicted menin-dependent, and the prediction rests on a paper nobody here can read.
Every source behind this entry (4)
  1. E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper

    The founding menin paper reports that the menin tumour suppressor protein is an essential oncogenic cofactor for MLL-associated leukemogenesis, and its abstract does not state which MLL fusion proteins were used.

    The menin tumor suppressor protein is an essential oncogenic cofactor for MLL-associated leukemogenesis. · Yokoyama A, Somervaille TC, Smith KS, Rozenblatt-Rosen O, Meyerson M, Cleary ML · Cell 2005
    PMID 16239140DOI
    What this evidence cannot show

    Identifiers taken from the NCBI esummary record fetched on 2026-09-19. This entry asserts nothing about the paper's content beyond its abstract, and deliberately does not guess which fusions were used - the standing rule for a known-but-unreadable source.

    Evidence that argues against this (1)
    • A companion literature established that menin binding requires MLL amino-terminal sequences rather than anything contributed by the partner, which if correct would make the fusion roster far less important than the three dependent entries assume - but that paper is itself unreadable by the same routes and is recorded as a separate bounded failure. Caslini C et al. 2007
  2. E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

    No open-access or repository route yields this paper's content or systems: PubMed esummary returns no PMC identifier, the Europe PMC core record returns pmcid null with isOpenAccess N and inEPMC N, and elink from the PMID to GEO returns zero records as does a GEO author search.

    Europe PMC REST core record and NCBI elink pubmed-to-gds for PMID 16239140 · Europe PMC and NCBI Entrez Programming Utilities 2026
    What this evidence cannot show

    Run on 2026-09-19 from a single network location, without institutional subscription access. A bounded unreadable for this session, not a permanent one: a subscribing reader, a library interlibrary loan, or an author request would each resolve it. The GEO author search used 'Yokoyama A[Author] AND menin' and would miss a deposition submitted under a different contributor name.

    Evidence that argues against this (1)
    • This beat found six of sixteen resolutions only through accessions printed in full-text data-availability statements, so a paper whose full text is unreachable is doubly disadvantaged - the route that most often works is itself gated behind the text - and an elink negative on such a paper is weaker than it looks. Rogic S et al. 2026
  3. E3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

    The question the three dependent entries need answered is whether menin dependence is a property of the retained KMT2A N-terminus and therefore shared across fusion partners, including septin and cytoskeletal partners, or a property of particular partners.

    The menin tumor suppressor protein is an essential oncogenic cofactor for MLL-associated leukemogenesis. · Yokoyama A, Somervaille TC, Smith KS, Rozenblatt-Rosen O, Meyerson M, Cleary ML · Cell 2005
    PMID 16239140DOI
    What this evidence cannot show

    This is a statement about what the graph needs, not a finding. It is recorded here so that a future cycle with subscription access knows exactly which sentence of the Methods to read: the construct list. The three dependent entries can be closed by one paragraph of text that this agent could not reach.

    Evidence that argues against this (1)
    • Reconstitution work has shown that different KMT2A fusion partners assemble distinct complexes, which argues that partner identity is not incidental and that a fusion roster from 2005 would be genuinely informative rather than a formality. Biswas D et al. 2011
  4. E5established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper

    PMID 16239140 has no PMC record and no free full-text route, but its abstract is 1,341 characters and states the central claim directly: oncogenic MLL fusion proteins retain stable association with menin through a high-affinity amino-terminal conserved binding motif, that interaction is required for initiation of MLL-mediated leukemogenesis, and menin is further required for maintenance. What the abstract does not state is which fusion proteins were used.

    PMID 16239140DOI
    What this evidence cannot show

    Abstract fetched from NCBI efetch by the coordinator on 2026-09-19 and read; full text not read and not reachable. Europe PMC returns no pmcid for this PMID, so the corrected PMC rule was applied and failed, which is the correct outcome here rather than an untried route. Recording what an abstract states is not the same as having checked how it was shown.

    Evidence that argues against this (2)
    • An abstract is the authors' own summary of their strongest reading, and this is a 2005 Cell paper whose framing set the field's direction for twenty years. Taking its headline as the sourced claim imports that framing wholesale: 'required for initiation' is a statement about the assays they chose, and the assays are exactly what cannot be read. The graph has been caught twice this year citing a paper's headline while its methods said something narrower. Cell 2005
    • The sibling bounded failure PMID 17671196 shows the limit of the corrected PMC rule rather than a route left untried: it DOES have a PMCID, PMC7566887, and both Europe PMC fullTextXML (HTTP 500) and efetch db=pmc return no readable body - the efetch response is 7,476 bytes of well-formed XML with the <body> element absent entirely. Verified by the coordinator. A PMCID is not a full text. NCBI E-utilities 2026
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