The compound in the only infant menin-inhibitor occupancy sample is revumenib, named in the abstract - and neither the dose nor the duration of exposure is recorded in the paper, the GEO record or the authors' repository
The drug the child was on is revumenib. How much of it, and for how long before the cells were taken, is written down nowhere we can find - and this project has already established that dose is exactly where menin-inhibitor chromatin results stop being comparable to one another.
The same thing, for a scientist
The dispatch premise for this beat was that the metadata 'never names the compound'. That is true of GEO and false of the paper: the **abstract** names it - *"In a sample that lineage switched during treatment with the menin inhibitor **revumenib**, the oncoprotein and menin are reduced to undetectable levels, but ENL ... persists"* - and the Results section repeats it. **Dose and exposure are a genuine absence.** The only concentration anywhere in the paper is `1 uM SNDX5613` and it belongs to an MV4;11 cell-line RNA-seq dataset re-used from Perner et al.; importing it into a patient claim would be a category error. No NCT number is given for this child. This matters because a menin-inhibitor occupancy result without a dose cannot be placed on the same axis as any other menin-inhibitor occupancy result.
What was searched, and where
- The full text of the paper at PMC11522475: every occurrence of
revumenib,SNDX,menin inhibitor,dose,mg,uMwas read in context 1. GSE252378_family.softin full: the only treatment string anywhere istreated with the Menin inhibitor2.- The authors' repository, which carries their processed tables, qPCR source data and the figure notebook: no dosing file 3.
The one concentration in the paper, in Methods Comparisons to RNA-seq: "We compared these log2FoldChange values from the MV4;11 sample treated with 1 uM SNDX5613 (Revumenib) to the PDX3, PDX4 and Patient 9 samples." That is a cell line, from a different study, and it is not this patient.
Why the dose absence is load-bearing and not pedantry
Revumenib's registrational dosing is intermittent oral dosing with a CYP3A4-dependent dose reduction, and its pharmacodynamic effect on oncoprotein-target gene expression was the trial's own response correlate 4. A patient sample is taken at one point on a fluctuating exposure curve. A chromatin occupancy measurement in such a sample is a snapshot at an unknown trough or peak, and the difference between those is exactly the axis on which this corpus has been trying to place menin-inhibitor occupancy results for several cycles.
Absence class
measured-not-reported. Somebody knows the dose and the exposure - it is in the treating institution's record and presumably in the study's source documents - and it was not written into the paper, the deposition or the repository. Closing it costs an email to the corresponding author, not an experiment.
| absence class | measured-not-reported |
|---|---|
| closes by | one email to the corresponding author |
| status | run |
what is absent
[ "dose of revumenib given to this patient", "duration of exposure before the 152985 draw", "interval between the 148752 and 152985 draws", "trial or protocol identifier for this patient" ]
what is present
{
"compound": "revumenib (SNDX-5613)",
"named_in": "the paper's abstract and Results; NOT in GEO"
}the one concentration in the paper
{
"value": "1 uM SNDX5613",
"belongs_to": "MV4;11 cell line RNA-seq re-used from Perner et al. 2023",
"do_not_import": true
}searched
[ "PMC11522475 full text", "GSE252378_family.soft (all 7,349 lines)", "github.com/DerekJanssens/MLL_oncoprotein_levels_NatComms file listing + README" ]
not searched
[ "the paper's Supplementary Information PDF", "the paper's Source Data file" ]
- This is the only infant menin-inhibitor chromatin occupancy sample anybody has found, and it will be quoted as such. Without a dose it cannot be compared to the VTP-50469 and MI-503 cell-line occupancy results this corpus already holds, so it extends the evidence base in breadth and not in depth.
- A reader who assumes the 1 uM figure applies to the patient will be comparing a saturating in-vitro concentration to an unknown in-vivo exposure and will conclude the drug is weaker in patients than it is.
- What dose of revumenib, on what schedule, and how many days before the 152985 draw?
- Was this child on the AUGMENT-101 protocol or on compassionate/expanded access? No registry identifier is given.
- Does the paper's Source Data file carry a per-patient treatment table? It was not opened here.
- E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
The paper's abstract names revumenib as the menin inhibitor this patient was treated with; no dose or exposure duration for the patient appears anywhere in the paper.
MLL oncoprotein levels influence leukemia lineage identities · Janssens DH, Duran M, Otto DJ, Wu W, Xu Y, Kirkey D, Mullighan CG, Yi JS, Meshinchi S, Sarthy JF, Ahmad K, Henikoff S · Nature Communications 15:9341 2024What this evidence cannot show
Bounded by the PMC full text plus the listed supplementary dataset titles; the Supplementary Information PDF and Source Data file were not opened, so a dosing table could in principle sit there. The caveat is that this is an absence in the text I read, not a bounded absence over every file the paper ships.
Evidence that argues against this (1)
- The paper's Source Data file and Supplementary Information were not opened here, and a paediatric dosing detail is exactly the kind of thing that lives in a supplementary patient table. This absence should be re-checked against those two files before it is quoted as complete. Janssens DH et al. 2024
- E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.dataset
The GEO records for all twenty libraries of this patient say only 'treated with the Menin inhibitor' and never name the compound, dose or exposure.
GSE252378_family.soft.gz - the per-sample SOFT records for GSE252378, read raw with line numbers · Janssens DH et al. · NCBI GEO FTP 2024What this evidence cannot show
Read from the raw SOFT family file. GEO has no dose field; a submitter wanting to record one would have to put it in characteristics or description, and neither does.
Evidence that argues against this (1)
- GEO's sample template has no field for drug exposure, so the omission is a property of the archive's schema rather than of this submission; the place a dose belongs is the publication, and this absence is therefore properly filed against the paper and not against the deposition. Janssens DH et al. 2024
- E3moderate confidence 3 of 5: One strong study, or several smaller consistent ones.dataset
The authors' public repository carries the processed signal tables, the qPCR source values and the figure notebook, and no dosing information.
MLL_oncoprotein_levels_NatComms - processed data tables and the figure-generation notebook for Janssens et al. 2024 · Janssens DH · GitHub / Zenodo (the paper's Code Availability statement) 2024What this evidence cannot show
A repository file listing plus the README; individual CSV contents were read only for the three signal tables used in this beat. A dose could be buried in a column of a file not opened.
Evidence that argues against this (1)
- A repository built to reproduce figures has no reason to carry clinical dosing, so its silence is expected rather than informative, and this evidence item is weak support for the absence by construction. Janssens DH 2024
- E4strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
Revumenib's clinical activity in KMT2A-rearranged leukaemia was correlated with reduced oncoprotein-target gene expression, which is the same readout class this deposit measures on chromatin.
The menin inhibitor revumenib in KMT2A-rearranged or NPM1-mutant leukaemia · Issa GC, Aldoss I, DiPersio J, Cuglievan B, Stone R, Arellano M, Thirman MJ, Patel MR, Dickens DS, Shenoy S, Shukla N, Kantarjian H, Armstrong SA, Perner F, Perry JA, Rosen G, Bagley RG, Meyers ML, Ordentlich P, Gu Y, Kumar V, Smith S, McGeehan GM, Stein EM · Nature 615:920-924 2023What this evidence cannot show
Phase 1 dose-escalation; the pharmacodynamic correlate is gene expression in blood/marrow, not chromatin occupancy, so the link to an occupancy measurement is by analogy.
Evidence that argues against this (1)
- Menin-inhibitor response in that trial was not uniform and MEN1 mutations emerged as a genetic resistance route, so an occupancy snapshot in a resistant relapse sample may be reporting a resistance mechanism rather than a dose effect. Perner F et al. 2023
the compound, named in the paper's abstract for this patient
the compound question only arises once the pair is read correctly
revumenib occupies the menin pocket that binds the KMT2A MBM motifs
no dose or exposure is recorded for this sample
an unrecorded exposure compounds an uninterpretable readout