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Overcoming Menin inhibitor resistance in AML cells with combinations including BET proteins and dual BRG1/BRM inhibitor [RNA-seq]

GSE315341 Homo sapiens (human) RNA-seq (gene expression) 60 samples Submitted 2026/03/03 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 60 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Homo sapiens (human)
Topic
Acute myeloid leukemiaThis series is part of our curated briefing on it.
Samples
60 samples: 30 conditions, mostly in duplicateGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
Overcoming menin inhibitor resistance in AML cells with combinations including BET proteins and a dual BRG1/BRM inhibitorBlood · 2026
Summary (written by the submitters)
Menin inhibitors (MI) disrupt the binding of Menin to MLL1 leading to repression of MLL1 or MLL1-fusion protein (FP) target genes, including reduced levels of HOXA9 and MEIS1 in AML with mtNPM1 or MLL1-r. While MIs are relatively well-tolerated and induce clinical remissions, these are often short-lived due to development of resistance followed by AML relapse.
Read the full summary ↓
Through repeated shocks with the MI SNDX-50469, a precursor tool compound to revumenib, followed by recovery, we developed MI-resistant (MITR) AML MV4-11 and OCI-AML3 cells. Present studies show that, compared to MI-sensitive parental cells, MITR cells exhibit an altered epigenome, transcriptome and proteome, without Menin mutations. Through a CRISPR screen, novel druggable MI co-enrichments were identified and targeted, including BRD4, SMARCA4, and CREBBP. Co-treatment with the MI and the SMARCA4/SMARCA2 (BRG1/BRM) inhibitor FHD-286 or the BET proteins inhibitor OTX015 (birabresib), synergistically induced in vitro lethality in MITR and MI-resistant AML cells expressing the mutant Menin (M327I), as well as in patient-derived (PD) AML cells with MLL1r or mtNPM1 that exhibited ex vivo resistance to MI. Compared to each drug alone, co-treatment with SNDX-5613 (revumenib) and FHD-286 or OTX015 and FHD-286 significantly reduced the in vivo AML burden and improved survival of the immune depleted mice, without inducing significant toxicity, in the xenograft models of MITR and MI-resistant PD MLLr AML cells. These findings highlight novel, targeted, drug combinations that overcome MI resistance in AML cells with MLL1r or mtNPM1.
Published in
Overcoming menin inhibitor resistance in AML cells with combinations including BET proteins and a dual BRG1/BRM inhibitor
Fiskus W, Mill CP, Issa GC et al. · Blood 2026 · PMID 41734382 · doi:10.1182/blood.2025031486
This dataset
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE315341_RAW.tar (it can run to tens of gigabytes).

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1395669 and SRA study SRP659041. Searching any of these in the dataset finder brings you back here.

Study design
30 conditions, mostly in duplicate
OCI-AML3 parental Control ×2 OCI-AML3 Parental 500 nM SNDX-50469 ×2 OCI-AML3 MITR Control ×2 OCI-AML3-MITR 500 nM SNDX-50469 ×2 MV4-11 parental Control ×2 MV4-11 Parental 500 nM SNDX-50469 ×2 MV4-11 MITR Control ×2 MV4-11-MITR 500 nM SNDX-50469 ×2 +22 more

Supports a between-group comparison across 60 samples.

How we read this: 30 replicated groups read from 60 sample titles; they account for 60 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

+ 20 more — browse all 60 samples with per-sample file links →

More Acute myeloid leukemia datasets

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.