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Menin inhibitor DS-1594b drives differentiation and induces synergistic lethality in combination with Venetoclax in acute myeloid leukemia cells with rearranged MLL1 and NPM1 mutations

GSE282741 Homo sapiens (human) RNA-seq (gene expression) 36 samples Submitted 2025/11/19 Platform GPL18573
At a glance

RNA-seq (gene expression) · human · 36 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
36 samples: 12 conditions, mostly in triplicateGroups 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
Menin inhibitor DS-1594b drives differentiation and induces synergistic lethality in combination with venetoclax in acute myeloid leukemia cells with rearranged mixed-lineage leukemia and mutated nucleophosmin-1Haematologica · 2026
Summary (written by the submitters)
MLL1 (KMT2A) rearrangements and NPM1 mutations are associated with acute leukemias whose pathogenesis is critically influenced by protein-protein interactions between menin and MLL1. We hypothesized that targeting the menin-MLL interaction using DS-1594b and targeting the antiapoptotic factor BCL-2 using venetoclax (ABT-199) may promote differentiation and enhance lethality in patients with MLL1-rearranged and NPM1-mutated leukemias.
Read the full summary ↓
We treated acute myeloid leukemia (AML) cell lines with MLL1 rearrangements, NPM1 mutations, and no mutations and samples from patients with primary AML with ABT-199 alone, DS-1594b alone, and their combination. We measured proliferation, viability, apoptosis, and differentiation using several assays, Western blotting, and BH3 profiling. Treatment with DS-1594b and ABT-199 exerted significant synergy, resulting in enhanced differentiation and inhibited proliferation across several cell lines. In the PDX model, DS-1594b single-agent treatment significantly extended survival (pv=***). Compared with DS-1594b monotherapy, the combination of DS-1594b and ABT-199 more profoundly reduced leukemic burden and prolonged mouse survival (pv=***). Overall, we observed synergistic effects on differentiation induction and proliferation inhibition, both in vitro and in vivo. Menin inhibition is the primary driver of transcription changes in this model, and impact on the expression of antiapoptotic regulators provide mechanistic explanation for the synergy observed between these drugs. Together, this underscores the promise of this combination strategy as a novel therapeutic approach for improving treatment outcomes in patients with these specific genetic alterations.
Published in
Menin inhibitor DS-1594b drives differentiation and induces synergistic lethality in combination with venetoclax in acute myeloid leukemia cells with rearranged mixed-lineage leukemia and mutated nucleophosmin-1
Ciaurro V, Sharlandjieva V, Skwarska A et al. · Haematologica 2026 · PMID 41195508 · doi:10.3324/haematol.2024.286833
This dataset
Open GSE282741 in finder → Find more human RNA-seq datasets → Acute myeloid leukemia landscape →
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.

Series matrix ↓
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 GSE282741_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
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.

Raw reads on ENA ↗

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 PRJNA1190338 and SRA study SRP547357. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41195508) ↗
Study design
12 conditions, mostly in triplicate
PDX_ABT ×3 PDX_COMBO ×3 PDX_CONTROL ×3 PDX_MENi ×3 MV411_ABT ×3 MV411_COMBO ×3 MV411_CONTROL ×3 MV411_MENi ×3 +4 more

Supports a between-group comparison across 36 samples.

How we read this: 12 replicated groups read from 36 sample titles; they account for 36 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
More Acute myeloid leukemia datasets

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