GSE252378 contains menin CUT&RUN in exactly one patient - a KMT2A::ENL lineage-switching pair under a menin inhibitor - and none in any of its eight KMT2A::AFF1 patients
The dataset that finally provides fusion-protein maps in real infant patients does not include the menin protein for the version of the fusion this project studies. Menin was measured in only one patient, who has a different fusion partner.
The same thing, for a scientist
**Bounded by reading every one of the 171 sample records in the deposit, not by a keyword search** [E1]. Menin libraries: `GSM8371009`, `GSM8371010` (sample 148752, infant B-ALL) and `GSM8371019`, `GSM8371020` (sample 152985, infant AML). GEO's description states 152985 is *paired with* 148752 - so these are two disease states of **one** lineage-switching patient, not two patients - and both carry **KMT2A-ENL**, both **treated with the menin inhibitor**, with no untreated arm in the deposit. **KMT2A::AFF1 patients in the same deposit with KMT2A N/C CUT&RUN and no menin track: eight** - `TB-05-1939`, `TB-92-0488`, `TB-98-6292` (St Jude, infant pre-B-ALL), `p179` (infant B-ALL), `p247` (pediatric B-ALL), `p279`, `p318`, `p454` (Texas Children's) [E1]. **So the index-fusion menin-occupancy absence this corpus already records survives this deposit, and is now bounded more tightly than before:** the assay exists, works on uncultured infant marrow, has been run by this group on infant material, and has simply not been pointed at a KMT2A::AFF1 patient. The absent experiment is a reagent swap away, and there are eight banked patients in one deposit that would supply the denominator. **A premise correction for the corpus.** The existing entry recording this deposit's menin arm describes 148752 and 152985 as two patient samples, which is accurate; a reader should not infer two patients. The menin measurement in this deposit has **n = 1 patient**.
What the absence does not cover
This is an absence within one deposit. It says nothing about menin CUT&RUN in KMT2A::AFF1 elsewhere, which other entries in this corpus bound separately. It is recorded because this deposit was the most likely place for the experiment to have been done quietly.
Name list, so a reader can judge the bound
The 171 !Sample_characteristics_ch1 and !Sample_description fields were read in full after transposing the series matrix column-wise. Antibody strings searched for: Menin, MEN1, Bethyl, A300-105A, A300-115A. The only hits are the four libraries named above, all annotated Rabbit Menin Bethyl Labs A300-.... No menin string appears in any KMT2A-AFF1 sample.
| script | analyses/q142-aff1-in-primary-infants/extract.py |
|---|---|
| status | run |
| result summary | 4 menin libraries, 1 patient, KMT2A-ENL, drug-treated; 0 menin libraries across 7 distinct KMT2A::AFF1 individuals. |
| n samples screened | 171 |
| absence class | never-measured |
| absence class basis | Bounded by reading every one of the 171 sample records. Menin libraries exist in the deposit but not for any KMT2A::AFF1 sample, so the measurement was never made in the index fusion. |
- Every menin-interface argument in this corpus for the index fusion still rests on cell lines or on other fusion partners; a menin inhibitor entering infant KMT2A::AFF1 trials has no primary occupancy baseline to be judged against.
- The banked material for seven KMT2A::AFF1 infants has already yielded working CUT&RUN in this laboratory - what stands in the way of a menin antibody being added?
- E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.dataset
The only menin libraries in GSE252378 are GSM8371009, GSM8371010, GSM8371019 and GSM8371020, all in one paired KMT2A-ENL lineage-switching patient treated with a menin inhibitor, while eight KMT2A::AFF1 patients in the same deposit have KMT2A N/C profiles and no menin track.
GSE252378 - AutoCUT&RUN and AutoCUT&Tag profiles of 36 MLL-rearranged leukemia samples (171 GSMs, hg38) · Janssens DH, Henikoff S (Fred Hutchinson Cancer Center / Van Andel Institute) · NCBI Gene Expression Omnibus 2024What this evidence cannot show
Bounded by the deposited metadata for 171 samples read in full. A menin library run but not deposited would be invisible. The eight-patient count includes p279 and p318, which are one patient in two states, so the number of distinct KMT2A::AFF1 individuals is seven.
Evidence that argues against this (1)
- The paper's figures may contain menin data for samples whose libraries are not separately deposited, and supplementary data files were not obtained; an absence in GEO is not an absence in the paper. Janssens DH et al. 2024
- E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper
The source paper reports that in the menin-inhibitor-treated lineage-switched sample the oncoprotein and menin fall to undetectable levels while ENL persists at oncoprotein-target loci including GMP-programme genes.
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
That result is in KMT2A::ENL, in one patient, under drug, with no untreated arm in the deposit. It is the nearest thing to an infant menin-occupancy result that exists and it is not in the index fusion.
Evidence that argues against this (1)
- 'Undetectable' in a CUT&RUN without spike-in is a statement about share, not amount - a global loss of signal and a redistribution of it are not distinguishable without a scaling reference, and this deposit has none. Janssens DH et al. 2024
no menin track in any KMT2A::AFF1 sample of the deposit
the absence survives this deposit and is now tightly bounded
171 sample records read in full
the only infant menin occupancy data are under a menin inhibitor in a different fusion
the primary-sample version closes this absence in the same run
sets the n for the menin arm
why the refutation tests cannot be run here