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Combining Menin and MEK inhibition to target poor prognosis KMT2A-rearranged RAS pathway-mutant acute myeloid leukemia

GSE281506 Homo sapiens (human) RNA-seq (gene expression) 42 samples Submitted 2026/05/29 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 42 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
42 samples: 14 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
Combining menin and MEK inhibition to target poor prognosis KMT2A-rearranged RAS pathway-mutant acute myeloid leukemiaBlood advances · 2026
Summary (written by the submitters)
KMT2A-rearranged acute leukemias are especially prevalent in the pediatric population. The KMT2A-fusion proteins drive leukemogenic gene expression through an interaction with a chromatin complex that includes the scaffold protein menin, giving rise to aggressive acute leukemias. RAS pathway mutations are common in pediatric leukemia.
Read the full summary ↓
In a cohort of 1605 patients enrolled on Children’s Oncology Group (COG) trials AAML0531 and AAML1031, we identified RAS pathway mutations in 43% of AML cases. The presence of RAS pathway mutations in KMT2A-r AML was associated with lower complete remission (CR) rate, poor event-free survival (EFS) and early relapses. We next sought to identify efficacious targeted drug combinations for this subset of childhood leukemia. We evaluated the combination of RAS/MAPK targeting using the MEK1/2 inhibitor selumetinib with the menin inhibitor revumenib. Treatment of acute leukemia cell lines and cultured leukemia cells from patient-derived xenograft (PDX) models resulted in a synergistic decrease in viability, promoted cell cycle arrest, and promoted downregulation of targets of MYC signaling by each drug alone and even more effectively with the combination. In vivo, the combination treatment of AML and ALL pediatric PDX models harboring KMT2A-r and RAS mutations reduced leukemia burden effectively compared with the single drug-treated cohorts. Tissues from treated mice showed a decrease in protein levels of MYC, P-ERK and MEIS1, highlighting effective target engagement of the drugs. Our preclinical study suggests a promising, readily translatable targeted treatment for KMT2A-r RAS pathway mutant leukemias.
Published in
Combining menin and MEK inhibition to target poor prognosis KMT2A-rearranged RAS pathway-mutant acute myeloid leukemia
Scheidegger N, Schneider C, Alexe G et al. · Blood advances 2026 · PMID 42085603 · doi:10.1182/bloodadvances.2025016208
This dataset
Open GSE281506 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 GSE281506_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 PRJNA1184160 and SRA study SRP544234. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42085603) ↗
Study design
14 conditions, mostly in triplicate
OCI-AML3 cells, DMSO, Day3, ×3 OCI-AML3 cells, VTP-50649, Day3, ×3 OCI-AML3 cells, VTP-50649+selumetinib, Day3, ×3 OCI-AML3 cells, DMSO, Day6, ×3 OCI-AML3 cells, VTP-50649, Day6, ×3 OCI-AML3 cells, VTP-50649+selumetinib, Day6, ×3 NOMO1 cells, DMSO, Day3, ×3 NOMO1 cells, VTP-50649, Day3, ×3 +8 more

Supports a between-group comparison across 40 samples.

How we read this: 14 replicated groups read from 42 sample titles; they account for 40 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

+ 2 more — browse all 42 samples with per-sample file links →

More Acute myeloid leukemia datasets

Search all human RNA-seq datasets in GEO →

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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.