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DNMT3A:R882H Is Not Required for Disease Maintenance in Primary Human AML, but Is Associated With Increased Leukemia Stem Cell Frequency [RNA-Seq]

GSE308271 Homo sapiens (human) RNA-seq (gene expression) 14 samples Submitted 2025/10/27 Platform GPL34284
At a glance

RNA-seq (gene expression) · human · 14 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
14 samples: 6 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
DNMT3A R882H Is Not Required for Disease Maintenance in Primary Human AML but Is Associated with Increased Leukemia Stem Cell FrequencyCancer discovery · 2026
Summary (written by the submitters)
Genetic mutations are being thoroughly mapped in human cancers, yet a fundamental question in cancer biology is whether such mutations are functionally required for cancer initiation, maintenance of established cancer, or both. Here, we study this question in the context of human acute myeloid leukemia (AML), where DNMT3A:R882 missense mutations often arise early, in pre-leukemic clonal hematopoiesis, and corrupt the DNA methylation landscape to initiate leukemia.
Read the full summary ↓
We developed CRISPR-based methods to directly correct DNMT3A:R882 mutations in leukemic cells obtained from patients. Surprisingly, DNMT3A:R882 mutations were largely dispensable for disease maintenance. Replacing DNMT3A:R882 mutants with wild-type DNMT3A did not impair the ability of AML cells to engraft in vivo, and minimally altered DNA methylation. Taken together, DNMT3A:R882 mutations are initially necessary for AML initiation, but are largely dispensable for disease maintenance. The notion that initiating oncogenes differ from those that maintain cancer has important implications for cancer evolution and therapy.
Published in
DNMT3A R882H Is Not Required for Disease Maintenance in Primary Human AML but Is Associated with Increased Leukemia Stem Cell Frequency
Köhnke T, Karigane D, Hilgart E et al. · Cancer discovery 2026 · PMID 41263425 · doi:10.1158/2159-8290.CD-24-1604
This dataset
Open GSE308271 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 GSE308271_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 PRJNA1330028 and SRA study SRP620959. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41263425) ↗
Study design
6 conditions, mostly in duplicate
SU575, DNMT3A Correction, Xenograft 156 ×3 SU372C, DNMT3A Correction, Xenograft 153 ×2 SU372C, DNMT3A ReMutation, Xenograft 153 ×2 SU540, DNMT3A Correction, Xenograft 155 ×2 SU540, DNMT3A ReMutation, Xenograft 155 ×2 SU575, DNMT3A ReMutation, Xenograft 156 ×2 SU575, DNMT3A ReMutation, Xenograft 157 ×1

Supports a between-group comparison across 13 samples.

How we read this: 6 replicated groups read from 14 sample titles; they account for 13 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

Search all human RNA-seq datasets in GEO →

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