Bounded failure: the one unresolved source that is actually about the index fusion
also called PMID 42537480 bounded failure · IGF2BP3 t(4;11) model systems · fusion mRNA abundance provenance
A 2026 paper on how the protein IGF2BP3 affects the amount of t(4;11) fusion message and protein is the only unreadable source in this beat that studies this project's own fusion. Its model systems are described only as model systems, it deposited nothing, and it cannot be read.
The same thing, for a scientist
`hyp-evicted-fusion-is-degraded-not-displaced` carries an evidence item hedged with *"Model systems rather than patient material, and the abstract does not quantify the effect sizes"* [E1]. Of the eight bounded failures in this beat, **this is the only one whose subject is t(4;11) itself** - every other unresolved source is an MLL-AF9, MOZ-TIF2, APL or non-leukaemic system whose distance from the index fusion is the finding. Here the distance is zero and the provenance is still unknown, which is a different and in some ways more frustrating result. No route returns anything: no PMCID in PubMed esummary or the Europe PMC core record, `isOpenAccess: N`, `inEPMC: N`, zero GEO by elink, zero SRA, BioSample or BioProject [E2]. A GEO keyword search on `IGF2BP3 AND leukemia` returns 43 series, and the leukaemia-relevant ones belong to identifiably different studies - an IGF2BP innate-immune-signalling pair, an IGF2BP3 stemness study, an ENCODE K562 iCLIP experiment and an oncofusion mRNA-stability study in mouse [E3]. None matches by title, and none was attributed, following the rule this beat adopted after the GSE200059 near-miss. The hypothesis this feeds - that an evicted fusion protein is degraded rather than displaced - is one of the more mechanistically specific ideas in this graph, and it turns on quantitative abundance measurements. *Model systems* could mean SEM and RS4;11, which would make the evidence directly relevant, or an overexpression construct in HEK293T, which would make it nearly irrelevant. The gap between those readings is the whole value of the citation.
Why the ambiguity is unusually costly here
Most provenance unknowns in this beat cost the graph a generalisation step: a result is real in MLL-AF9 and its transfer to KMT2A::AFF1 is unproven. This one costs something different. The claim is about the abundance of the fusion transcript and protein, and abundance measurements are notoriously sensitive to whether the fusion is expressed from its endogenous locus or from a transfected plasmid.
- Endogenous (SEM, RS4;11, MV4-11): abundance reflects real regulation, and an IGF2BP3 effect is a real post-transcriptional control on the oncoprotein.
- Ectopic (HEK293T or similar): abundance reflects promoter strength and plasmid copy number, and an RNA-binding-protein effect may be an artefact of an unnatural 3' UTR context.
IGF2BP3 acts through m6A-dependent transcript stabilisation and binds 3' UTRs, so the construct's UTR is decisive. Nothing in the record says which was used.
Where this leaves the hypothesis
hyp-evicted-fusion-is-degraded-not-displaced should keep this evidence item at low confidence and add the bound: the systems are unnamed, unreadable and undeposited, and the distinction between endogenous and ectopic expression is not recoverable. The hypothesis does not fall - it has other support - but this particular item cannot carry weight until someone reads the paper.
The cheap next step is a single library request. Leuk Res is a subscription journal with wide institutional coverage, and this is a short paper.
| script | none - Europe PMC, NCBI elink, GEO keyword search |
|---|---|
| status | run |
| result summary | Unresolved. No PMCID, no deposition, no readable text. The only bounded failure in the beat whose subject is the index fusion itself. The decisive unknown is whether the fusion was expressed endogenously or ectopically, which determines whether an abundance measurement means anything. |
| what would resolve it | A library copy of Leuk Res 2026, reading one sentence of the Methods: whether the t(4;11) fusion was endogenous or transfected. |
| resolution class | bounded failure |
| note | the only unresolved source in this beat studying the index fusion |
inputs
[ "PMID 42537480" ]
routes tried
[ "PubMed esummary (no pmc)", "Europe PMC core (pmcid null, isOpenAccess N, inEPMC N)", "elink pubmed->gds, sra, biosample, bioproject (0 each)", "esearch db=gds 'IGF2BP3 AND leukemia' (43 series, top 8 title-checked, none matching)" ]
entries affected
[ "hyp-evicted-fusion-is-degraded-not-displaced" ]
- IGF2BP3 stabilises a large set of transcripts through m6A reading, so an intervention aimed at it to lower fusion abundance would lower much else and has no obvious therapeutic window.
- If the abundance effect was measured on a transfected construct, then a strategy built on it is built on plasmid copy number, and the failure would only appear after considerable investment.
- Lowering fusion oncoprotein abundance without eliminating it may select for cells that upregulate the fusion, which is a resistance route this graph has not modelled for any modality.
- Was the t(4;11) fusion expressed from its endogenous locus or from a construct? An abundance claim means opposite things in the two cases.
- Does IGF2BP3 control fusion transcript abundance in SEM or RS4;11 specifically? If so this is a direct handle on oncoprotein dosage in the index disease, and it would be one of very few.
- E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper
The paper reports the influence of IGF2BP3 on t(4;11) fusion mRNA and protein abundance, and its abstract describes model systems without naming them and does not quantify the effect sizes.
Influence of IGF2BP3 on t(4;11) fusion mRNA and protein abundance. · Hanewald T, Benz T, Marschalek R · Leuk Res 2026What this evidence cannot show
Identifiers taken from the NCBI esummary record fetched on 2026-09-19. This entry asserts nothing about the paper's systems and does not guess whether the fusion was expressed endogenously or ectopically.
Evidence that argues against this (1)
- IGF2BP3 has an established role in leukaemia stemness independent of any fusion transcript, so an effect on t(4;11) fusion abundance needs to be separated from a general effect on the leukaemic transcriptome before it supports a fusion-specific degradation model. Dietsche L et al. 2024
- E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
No full text or deposition is reachable: 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, SRA, BioSample and BioProject returns zero records.
Europe PMC REST core record and NCBI elink for PMID 42537480 · Europe PMC and NCBI Entrez Programming Utilities 2026What this evidence cannot show
Run on 2026-09-19 from a single network location without subscription access. A 2026 paper may acquire a PMC record later under a funder mandate, so this should be retried in a future cycle. A short mechanistic paper may legitimately have no sequencing to deposit, in which case no repository route would ever resolve it and only the text will do.
Evidence that argues against this (1)
- Two other 2026 subscription papers in this beat resolved completely from depositions their authors had made, so recency alone does not predict failure and the absence of a deposition here is a choice rather than a norm. Bröchtel S et al. 2026
- E3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
A GEO keyword search on IGF2BP3 and leukemia returns 43 series whose leukaemia-relevant members belong to identifiably different studies - an IGF2BP innate-immune-signalling pair, an IGF2BP3 stemness study, an ENCODE K562 iCLIP experiment and a mouse oncofusion mRNA-stability study - none matching this paper by title.
NCBI esearch db=gds keyword query 'IGF2BP3 AND leukemia' · NCBI Gene Expression Omnibus 2026What this evidence cannot show
Run on 2026-09-19; the top eight hits were checked by title and none matches. The remaining 35 were not individually title-checked, so this is a bounded rather than an exhaustive negative. The exclusions follow this beat's attribution rule - topic match is not attribution - established after a topic-exact series in another entry proved to belong to a different paper.
Evidence that argues against this (1)
- One of the excluded series concerns chromosomal-rearrangement-enhanced mRNA stability in oncofusions, which is close enough in subject that it deserves reading on its own merits even though it is not this paper's deposition. Hanewald T et al. 2026
bounded failure; endogenous versus ectopic expression is not recoverable and decides the claim
- related to →KMT2A::AFF1 (MLL-AF4), t(4;11)(q21;q23)
the only unresolved source in this beat whose subject is the index fusion
bounded failure in the unstated-system worklist