No KMT2A fusion junction peptide has ever been reported - the one measurement that would prove the protein exists has not been published
also called junction peptide bounded absence · nobody has detected a KMT2A fusion protein by mass spectrometry
The short piece of protein that straddles the join is the only thing that can prove a fusion protein is really there, and our calculation says it is measurable. Searching the published literature for anyone reporting one in a KMT2A leukemia returns nothing at all.
The same thing, for a scientist
`ana-junction-peptide-detectability-kmt2a-fusions` establishes that a proteome-unique junction peptide exists and is in a detectable mass range for 47 of 48 in-frame modelled KMT2A fusion junctions. This entry records the matching literature search. **`(KMT2A[tiab] OR MLL[tiab] OR "MLL-AF4"[tiab] OR "MLL-AF9"[tiab]) AND ("junction peptide"[tiab] OR "junction-spanning"[tiab] OR "fusion peptide"[tiab] OR "fusion-specific peptide"[tiab])` returns 0 records**, with the query translation confirming PubMed parsed every term as written. Broader queries return only method papers and unrelated proteomics. This is a **bounded absence of testing**, not a negative result: the proteogenomic tooling for junction-peptide search has existed since at least 2019 [E2], and the obstacle this beat identified (a tryptic site at the junction) is a search-parameter setting, not a physical limit. The practical consequence is that **every protein-level claim about a KMT2A fusion in this graph rests on antibodies, and none rests on a species-resolved identification of the fusion polypeptide itself.**
The queries, exactly as run
Run 2026-09-20 against PubMed eutils. Counts and query translations were read back before any negative was recorded, per the standing rule that a surprising 0 means checking querytranslation first.
| query | count |
|---|---|
(KMT2A OR MLL OR "MLL-AF4" OR "MLL-AF9")[tiab] AND ("junction peptide" OR "junction-spanning" OR "fusion peptide" OR "fusion-specific peptide")[tiab] | 0 |
"junction peptide"[tiab] AND (leukemia OR leukaemia)[tiab] | 2 (1980 retrovirus glycoprotein; 1996 CBFB-MYH11 protein, antibody-based) |
(KMT2A OR MLL)[tiab] AND fusion[tiab] AND (mass spectrometry OR proteomics OR proteomic)[tiab] | 20, none reporting a junction peptide |
(KMT2A OR MLL)[tiab] AND ("parallel reaction monitoring" OR "selected reaction monitoring" OR "multiple reaction monitoring" OR "targeted proteomic")[tiab] | 4, all pharmacokinetics or unrelated analytes |
"BCR-ABL"[tiab] AND ("junction peptide" OR "fusion peptide")[tiab] AND mass spectrometry[tiab] | 0 |
The last row matters: BCR::ABL1 is the most measured fusion protein in medicine and it has no published junction-peptide identification either. So this is not a KMT2A-specific neglect; it is a gap in how the whole field verifies fusion proteins.
The 20 records in the third row were title-checked individually. They are menin-inhibitor pharmacology, interactome and drug-resistance proteomics in KMT2A-r lines - studies that measure the proteome of a cell carrying a fusion, never the fusion polypeptide as an identified species.
What was found instead, and why it does not close the gap
Two adjacent literatures exist and neither substitutes.
Proteogenomic junction-peptide tooling. FusionPro and its successors build fusion-augmented search databases specifically so that junction peptides can be identified 2. The infrastructure is not the limiting factor.
Protein-level fusion detection by sandwich immunoassay. The EuroFlow flow-cytometric immunobead assay captures with an antibody against one partner and detects with an antibody against the other, and an assay of this design was built for MLL-AF4 3. That is a genuinely fusion-attributable protein measurement and it is recorded as such in concept-attribution-designs-that-actually-work. But it is a yes/no diagnostic on a lysate. It gives no sequence, no modification state, no interaction partner and no chromatin position, so it cannot adjudicate any of the mechanistic claim classes this beat audits.
The gap is therefore precise: the field can tell that a KMT2A fusion protein is present in a patient sample, and cannot tell which protein any given molecular measurement came from.
Bounded rejection: what was searched and set aside
Recorded so a future cycle repeats the decision rather than only the search.
- PMID 8818654, Identification of the chimeric protein product of the CBFB-MYH11 fusion gene in inv(16) leukemia cells (1996). Title is squarely on-beat. Set aside because the identification is by antibody and apparent molecular weight, not by peptide sequence. It is, however, the closest published analogue of the design this beat wants and would be worth reading in full if the reciprocal-product assay is ever built.
- PMID 42400790, Mass Spectrometry-Based Validation of Chimeric RNAs (2026). A protocol for exactly this problem in the general case. Cited as counter-evidence in the analysis entry rather than as support, because it treats junction-peptide identification as requiring deliberate validation - which is an argument for caution about any future null, not evidence about KMT2A.
- The CPTAC-style discovery proteomics of KMT2A-r leukaemia was not enumerated deposition-by-deposition in this beat. A GEO/PRIDE-level sweep for raw files from SEM, RS4;11 and MV4-11, re-searched with a fusion-augmented database and two missed cleavages, is the obvious next step and was out of scope here. Until that is done, the absence recorded above is an absence in the published literature, not in the deposited data.
| status | run |
|---|---|
| absence class | measured-not-searched |
| junction peptides reported for any kmt2a fusion | 0 |
| what would close it | exp-junction-peptide-prm-assay-kmt2a-fusions |
| computed target | ana-junction-peptide-detectability-kmt2a-fusions |
| not swept | PRIDE/ProteomeXchange raw files from SEM, RS4;11, MV4-11 re-searched against a fusion-augmented database with 2 missed cleavages |
| absence class previous freetext | absence of testing in the published literature; deposited raw data not swept |
| absence class basis | The entry's own data block says PRIDE raw files were not swept. PXD009338 is an affinity purification in which an MLL fusion is the BAIT; a junction-spanning peptide has no entry in a standard human database and would go unassigned rather than be reported absent. |
| absence class assigned | 2026-09-21 (cycle 47, king) |
queries — the numbers behind the chart
[
{
"query": "(KMT2A[tiab] OR MLL[tiab] OR \"MLL-AF4\"[tiab] OR \"MLL-AF9\"[tiab]) AND (\"junction peptide\"[tiab] OR \"junction-spanning\"[tiab] OR \"fusion peptide\"[tiab] OR \"fusion-specific peptide\"[tiab])",
"records": 0,
"querytranslation_checked": true
},
{
"query": "\"junction peptide\"[tiab] AND (leukemia[tiab] OR leukaemia[tiab])",
"records": 2,
"note": "PMID 6254670 (1980, retroviral glycoprotein) and PMID 8818654 (1996, CBFB-MYH11 chimeric protein by antibody) - neither is a fusion junction peptide identification"
},
{
"query": "(KMT2A[tiab] OR MLL[tiab]) AND fusion[tiab] AND (mass spectrometry[tiab] OR proteomics[tiab] OR proteomic[tiab])",
"records": 20,
"note": "all title-checked; all measure the proteome of a cell carrying a fusion, none identify the fusion polypeptide"
},
{
"query": "\"BCR-ABL\"[tiab] AND (\"junction peptide\"[tiab] OR \"fusion peptide\"[tiab]) AND mass spectrometry[tiab]",
"records": 0,
"note": "the most-measured fusion protein in medicine has no published junction-peptide identification either"
},
{
"query": "(KMT2A[tiab] OR MLL[tiab]) AND (\"parallel reaction monitoring\"[tiab] OR \"selected reaction monitoring\"[tiab] OR \"multiple reaction monitoring\"[tiab] OR \"targeted proteomic\"[tiab])",
"records": 4,
"note": "revumenib liver-microsome pharmacokinetics and three unrelated analytes"
}
]- If a junction-peptide assay is built and reported negative in a patient sample, the likeliest causes are a wrong breakpoint model, zero missed cleavages in the search, or abundance below the limit of detection - none of which mean the fusion protein is absent. A negative used to de-escalate therapy would be dangerous.
- Building the assay creates a pharmacodynamic biomarker that a sponsor could adopt before it is validated against outcome. A fusion-protein level that falls under drug is not itself evidence of clinical benefit.
- Does a junction peptide sit unremarked in already-deposited raw files? A re-search of public SEM and RS4;11 proteomes against a fusion-augmented database costs nothing and would convert this absence of testing into a real result in either direction.
- Why has no fusion oncoprotein - including BCR::ABL1 - had its junction peptide reported? If the answer is abundance rather than neglect, that is a quantitative claim somebody should state, and it would change what this graph should ask for.
- E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
A PubMed search combining KMT2A/MLL fusion terms with junction-peptide terminology returns zero records, with the query translation confirming the parser did not rewrite the query.
What this evidence cannot show
A counted absence is only as good as its symbol set. 'MLL' and 'KMT2A' were both searched, as were the hyphenated fusion spellings MLL-AF4 and MLL-AF9, but the double-colon forms (KMT2A::AFF1) and partner-only phrasings were not exhaustively enumerated, and a paper that reports a junction peptide in a supplementary table without saying so in title or abstract is invisible to this method. The absence is bounded to title/abstract text.
Evidence that argues against this (1)
- A protein-level, fusion-attributable detection method for MLL-AF4 does exist and was published - the flow-cytometric immunobead sandwich assay - so 'nobody has measured the fusion protein' would be too strong a reading of this absence. What is absent is a sequence-resolved identification, not any protein-level detection. Dekking E et al. 2010
- E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
Software for constructing fusion-augmented protein databases and identifying junction peptides from chimeric transcripts has been published and benchmarked, so the absence of KMT2A junction-peptide reports is not a tooling gap.
FusionPro, a Versatile Proteogenomic Tool for Identification of Novel Fusion Transcripts and Their Potential Translation Products in Cancer Cells. · Kim CY, Na K, Park S, et al. · Mol Cell Proteomics 2019What this evidence cannot show
A tool existing is not the same as it having been applied to this disease, and this beat found no application of it to KMT2A-rearranged leukaemia. Tool availability bounds the interpretation of the absence; it does not fill it.
Evidence that argues against this (1)
- Junction-peptide identification is presented in the methods literature as a validation step needing dedicated design rather than as a routine discovery output, which is a reason to expect low yield and to treat a future null as uninformative unless the assay was targeted. Zahra S et al. 2026
- E3moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper
A flow-cytometric immunobead sandwich assay that captures with an antibody against one fusion partner and detects with an antibody against the other was designed for MLL-AF4 among six other leukaemia fusions.
Detection of fusion genes at the protein level in leukemia patients via the flow cytometric immunobead assay. · Dekking E, van der Velden VH, Böttcher S, et al. · Best Pract Res Clin Haematol 2010What this evidence cannot show
The MLL-AF4 assay is stated in a review of the assay family; the primary validation papers this beat could find are for BCR-ABL and PML-RARA, not for MLL-AF4, so the MLL-AF4 assay's sensitivity, specificity and cohort performance were not verified here. `"immunobead"[tiab] AND ("MLL"[tiab] OR "AF4"[tiab])` returns exactly this one record.
Evidence that argues against this (1)
- The same assay family's primary publication is for BCR-ABL, where the fusion partners are both abundant and the epitopes well characterised; whether a two-antibody sandwich achieves usable sensitivity for a ~240 kDa nuclear protein present at lower abundance than wild-type AF4 is not established by the review. Weerkamp F et al. 2009
the computation says the peptide is measurable; this entry records that nobody has reported one
the same gap one layer down: no fusion polypeptide has ever been identified as a species, so no modification on one can have been
- related to →KMT2A::AFF1 (MLL-AF4), t(4;11)(q21;q23)
no protein-level sequence-resolved identification of this fusion exists in the literature
the experiment that converts this absence of testing into a result
Names the accession that entry's own data block asks for. It records not_swept as PRIDE/ProteomeXchange raw files re-searched against a fusion-augmented database and names none; PXD009338 is a submission in which an MLL fusion is the BAIT, making it the most likely public location of a junction peptide.
Uses it as the worked case: the entry itself states its raw data were not swept and names no archive, and a PRIDE v3 keyword search returns candidate datasets from SEM, RS4;11 and MV4-11 immediately.
sharpens the absence: for the 1444/1445 architecture no missed cleavage is needed
three annotated breakpoints means three junction peptides, which is part of why none has been reported
instrument mismatch named: a claim about mass-spectrometry datasets bounded by PubMed abstracts. PRIDE swept this cycle and the archive half now has accessions
the archive the entry named as not swept, swept: three human MLL-AF4 projects with instruments and dates, and the absence still holds