Treating the five menin inhibitors as one drug, when a 2026 title says they are not
also called menin inhibitor class effect · revumenib ziftomenib bleximenib enzomenib differences · class assumption infant ALL
This project reasons about five menin inhibitors as if they were interchangeable because they all block the same pocket. A 2026 paper from the Perth infant-leukaemia group states in its title that they show different sensitivity in infant leukaemia cells - and the paper itself cannot be read anywhere, so we know the claim exists and not what it says.
The same thing, for a scientist
The menin-interface hypothesis that organises this graph treats revumenib, ziftomenib, bleximenib, enzomenib and pinometostat's menin-directed peers as probes of one target. A title-level assertion published in June 2026 by Dymock, Oommen, Malinge, Cheung and Kotecha states that menin inhibitors display **differential in vitro sensitivity in KMT2A-rearranged infant acute lymphoblastic leukemia** [E1]. That paper has **no abstract in PubMed and none in Europe PMC**, is not open access, is not in PMC, and the publisher page returns HTTP 403 to automated retrieval; three routes were tried on 2026-09-19 and all failed [E1][E2]. This is therefore a **bounded unreadable**, not a finding, and this entry deliberately does not speculate on what the paper reports. What can be said is what the risk is if the title means what it says: every class-level inference in this graph - that a resistance mutation found against one agent predicts failure of another, that a potency measured with one compound transfers, that a trial with one agent de-risks the others - would need re-examination for infant ALL specifically. The surrounding literature already gives two independent reasons to expect class heterogeneity: response to revumenib in KMT2A-rearranged **ALL** is described as quick and highly synergistic with DOT1L inhibition, in contrast to KMT2A-rearranged AML [E3], and single-agent menin inhibitor efficacy is short-lived because of readily emerging acquired resistance in vitro and in patients [E3].
What was tried, and what it returned
| Route | Result |
|---|---|
| NCBI efetch XML, PMID 41711432 | record present, full metadata, *** NO ABSTRACT *** |
| Europe PMC REST core search, EXT_ID:41711432 | record present, abstractText absent, isOpenAccess: N, inEPMC: N, pmcid: null |
| Europe PMC fullTextXML | not applicable, no PMC identifier |
| Crossref works API, DOI 10.1080/10428194.2026.2631099 | title only, no abstract element |
| Publisher, tandfonline.com | HTTP 403 |
Citation as fetched: Dymock SCC, Oommen J, Malinge S, Cheung LC, Kotecha RS. Leuk Lymphoma 2026;67(7):1607-1611. DOI 10.1080/10428194.2026.2631099. The DOI was read from the article's own PubmedData/ArticleIdList and cross-checked against esummary articleids; both agree.
Note also that the efetch ArticleTitle element truncates at the first italic run if read with a naive text accessor: a first pass returned 'Menin inhibitors display differential ' and dropped 'in vitro sensitivity in KMT2A-rearranged infant acute lymphoblastic leukemia'. The full title above was recovered by concatenating all text nodes including markup children. This is the same markup-loss failure the brief warns about, occurring in a title rather than an abstract.
Why a class assumption is fragile here even without this paper
Three mechanisms by which nominally same-target inhibitors diverge, all live for this class:
- Binding mode within the pocket. Menin inhibitors are not a single chemotype. Different scaffolds contact different subsets of pocket residues, which is exactly why resistance mutations at particular residues confer different degrees of cross-resistance rather than uniform class failure.
- Off-target activity. At the concentrations used in cell assays, potency differences can reflect polypharmacology rather than menin engagement, and a cell-line IC50 ranking is not a target-engagement ranking.
- Cellular context. The lymphoid setting differs from the myeloid one in the kinetics and depth of response 3. A class effect established in KMT2A-rearranged AML, where most clinical experience sits, is not automatically a class effect in infant ALL.
The graph should therefore carry menin-inhibitor claims with the agent named, and should treat 'menin inhibitors' as a shorthand that requires justification whenever a claim turns on it.
What would resolve it
Any one of: an institutional subscription copy of the Leuk Lymphoma article; correspondence with the Telethon Kids / Perth group; or an independent cross-panel comparison of revumenib, ziftomenib, bleximenib and enzomenib on the same infant KMT2A-rearranged cell lines and PDX cultures with matched target-engagement readouts. The third is the one this project could run. The cell lines are named in the adjacent Perth-linked literature (PER-485, PER-703, PER-494, KOPN-8 among them) and are the same panel on which the MCL1 result was obtained.
| kind | resistance |
|---|---|
| severity | structural: it affects how every menin-inhibitor claim in this graph should be scoped, not the safety of any one agent |
| status | unresolved; the primary source is unreadable |
| mitigation | name the agent in every menin-inhibitor claim; run a matched cross-agent panel on infant KMT2A-r lines and PDX cultures; obtain the article through an institutional subscription or by contacting the authors |
affects
[ "drug-revumenib", "drug-ziftomenib", "drug-bleximenib", "drug-enzomenib" ]
unreadable record
{
"pmid": "41711432",
"doi": "10.1080/10428194.2026.2631099",
"journal": "Leuk Lymphoma",
"volume": "67",
"issue": "7",
"pages": "1607-1611",
"routes_tried": [
"NCBI efetch XML",
"Europe PMC core search",
"Europe PMC fullTextXML",
"Crossref works",
"publisher tandfonline.com"
],
"date_checked": "2026-09-19",
"title": "Menin inhibitors display differential in vitro sensitivity in KMT2A-rearranged infant acute lymphoblastic leukemia.",
"authors": "Dymock SCC, Oommen J, Malinge S, et al.",
"venue": "Leuk Lymphoma",
"year": 2026,
"title_provenance": "Title/authors/venue backfilled from PubMed esummary on 2026-09-20 because this citation stored a bare PMID with no title, which made it unscoreable by verify-citations.py. BACKFILLING IS NOT VERIFICATION: it confirms the PMID resolves to a real paper, not that this is the right paper for the claim. That still requires reading."
}- If the class assumption fails, a negative infant trial of one menin inhibitor will wrongly close the door on the mechanism, and a positive one will wrongly open it for four other molecules.
- Cross-resistance patterns characterised in KMT2A-rearranged AML may not transfer to infant ALL, so a resistance-monitoring plan built on AML data could miss the relevant mutations.
- Reading an IC50 ranking as a target-engagement ranking confuses potency with polypharmacology, and a differential-sensitivity result could be an off-target result.
- This graph's own reasoning is the exposure here: several entries generalise from one agent to the class, and if the title is right those generalisations are the error, not the drug.
- Do revumenib, ziftomenib, bleximenib and enzomenib rank the same way across a panel of infant KMT2A-rearranged cell lines and PDX cultures at matched target engagement?
- Does a resistance mutation selected against one menin inhibitor confer cross-resistance to the others in a lymphoid, infant-derived context, or only in the myeloid lines where it was characterised?
- What does PMID 41711432 actually report? Until someone reads it, this graph is reasoning about a claim it has only seen the title of.
- E1weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paper
A 2026 report from the Perth infant-leukaemia group asserts in its title that menin inhibitors display differential in vitro sensitivity in KMT2A-rearranged infant acute lymphoblastic leukaemia.
Menin inhibitors display differential in vitro sensitivity in KMT2A-rearranged infant acute lymphoblastic leukemia. · Dymock SCC, Oommen J, Malinge S, Cheung LC, Kotecha RS · Leuk Lymphoma 2026What this evidence cannot show
TITLE ONLY. No abstract is available from NCBI efetch or Europe PMC; the article is not open access, has no PMC identifier, and the publisher page returned HTTP 403 on 2026-09-19. Crossref returns no abstract element. Nothing about which inhibitors were compared, in which cells, at what concentrations or with what result is known to this graph, and nothing is inferred here. This is recorded as a bounded unreadable.
Evidence that argues against this (1)
- A title is an author's framing and can overstate; 'differential sensitivity' could describe a two-fold IC50 spread within a panel, which would be unremarkable, or a categorical difference, which would not. Without the data the claim cannot be weighted, and this graph should not act on it. Stutterheim J et al. 2025
- E2moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
PMID 41711432 has no retrievable abstract through NCBI efetch or Europe PMC and is not available in PMC, checked on 2026-09-19.
Europe PMC REST service: article and full-text-XML availability check, run 2026-09-19 · Q7-clinical-infant beat (this graph) · Europe PMC 2026What this evidence cannot show
Availability can change: journals deposit abstracts late, and Leuk Lymboma articles sometimes acquire abstracts on MEDLINE indexing. A check at a later date may succeed and this entry should be revisited rather than treated as permanent.
Evidence that argues against this (1)
- Two of the three papers this graph previously recorded as unreadable - PMIDs 42246204 and 40016188 - proved fully readable via Europe PMC full-text XML on the same day this one failed, so 'unreadable' is a statement about one retrieval attempt and not a stable property. Karsa M et al. 2026
- E3moderate confidence 3 of 5: One strong study, or several smaller consistent ones.review
Menin and DOT1L inhibitor efficacy as single agents is short-lived because of readily emerging acquired resistance in vitro and in patients on trial, and in KMT2A-rearranged ALL, in contrast to KMT2A-rearranged AML, the response to revumenib is quick and highly synergistic with the DOT1L inhibitor pinometostat.
KMT2A-rearranged acute lymphoblastic leukemia in infants: current progress and challenges. · Stutterheim J, Van der Sluis IM, Vrenken KS, Pieters R, Stam RW · Haematologica 2025What this evidence cannot show
A review's summary of its references 44-47; the underlying primary reports were not retrieved by this beat and should be fetched before this claim is used as primary evidence. The ALL-versus-AML contrast is asserted, not quantified. Read in the open-access full text at PMC12399962.
Evidence that argues against this (1)
- If ALL and AML differ this much in response to the same agent, then class-level reasoning across diseases is already unsafe in this graph independently of whether individual agents differ from each other. Dymock SCC et al. 2026
- E4moderate confidence 3 of 5: One strong study, or several smaller consistent ones.review
A phase II trial of the menin inhibitor revumenib in infant ALL (NCT05761171) is listed among current and planned trials, alongside a venetoclax trial (NCT06317662).
KMT2A-rearranged acute lymphoblastic leukemia in infants: current progress and challenges. · Stutterheim J, Van der Sluis IM, Vrenken KS, Pieters R, Stam RW · Haematologica 2025What this evidence cannot show
Reported in a 2025 review's table. Registry status, arms, eligibility and any withdrawal or suspension must be checked against the raw ClinicalTrials.gov API, including the whyStopped field, before any claim is made about this trial; this beat did not do so.
Evidence that argues against this (1)
- A single-agent-class trial in infants that is designed on the assumption of a class effect will, if the class effect does not hold, produce a result attributable to one molecule and be read as a result about menin inhibition. Dymock SCC et al. 2026
a 2026 title asserting differential in vitro sensitivity among menin inhibitors in KMT2A-rearranged infant ALL bears directly on this risk and is unreadable by all four routes
class-level reasoning about this agent may not hold in infant KMT2A-rearranged ALL
class-level reasoning about this agent may not hold in infant KMT2A-rearranged ALL
class-level reasoning about this agent may not hold in infant KMT2A-rearranged ALL
class-level reasoning about this agent may not hold in infant KMT2A-rearranged ALL
the shared target whose inhibitors may not behave alike in infant ALL
PMID 41711432 remains unreadable on 2026-09-19 across five routes
the setting in which the class assumption is asserted to fail
the unreadable differential-sensitivity report that raises the class question