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An epigenetic-signaling pathway interplay re-wires transcriptional program to induce therapeutic differentiation of AML

GSE249879 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2025/01/09 Platform GPL13112
At a glance

RNA-seq (gene expression) · mouse · 12 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
Mus musculus (mouse)
Samples
12 samples: 3 × ER-HoxA9_cells_Vehicle vs 3 × ER-HoxA9_cells_GSK-LSD1 vs 3 × ER-HoxA9_cells_LY20903014 vs 3 × ER-HoxA9_cells_ComboGroups 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
Perturbing LSD1 and WNT rewires transcription to synergistically induce AML differentiationNature · 2025
Summary (written by the submitters)
Differentiation therapy has proven to be curative for the rare acute myeloid leukemia (AML) subtype, the acute promyelocytic leukemia (APL). However, whether differentiation induction is a generalizable therapeutic approach for AML and beyond remains incompletely understood. In this study, we demonstrate that simultaneous inhibition of the histone demethylase LSD1 (LSD1i) and the Wnt pathway GSK3β kinase (GSK3βi) robustly promotes therapeutic differentiation of established AML cell lines and primary human AML cells, as well as reducing tumor burden in a xenograft mouse model.
Read the full summary ↓
Mechanistically, this combination promotes differentiation by activating genes in the type I interferon pathway (IFN-I) via inducing expression of IRF7 (LSD1i) and b-catenin (GSK3i) and their selective co-occupancy at targets such as STAT1, which is necessary for combination-indued differentiation. Combination treatment also suppresses the canonical, pro-oncogenic Wnt pathway and cell cycle genes. Importantly, analysis of AML patient datasets suggests a correlation between the combination-induced transcription signature and better prognosis, highlighting clinical potential of this strategy. Collectively, our findings suggest that this combination strategy re-wires transcriptional programs to suppress stemness and to promote differentiation, which may have important therapeutic implications for AML and Wnt-driven cancers beyond AML.
Published in
Perturbing LSD1 and WNT rewires transcription to synergistically induce AML differentiation
Hosseini A, Dhall A, Ikonen N et al. · Nature 2025 · PMID 40240608 · doi:10.1038/s41586-025-08915-1
This dataset
Open GSE249879 in finder → Find more mouse RNA-seq datasets →
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 GSE249879_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 PRJNA1051076 and SRA study SRP477326. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40240608) ↗
Study design
3 × ER-HoxA9_cells_Vehicle vs 3 × ER-HoxA9_cells_GSK-LSD1 vs 3 × ER-HoxA9_cells_LY20903014 vs 3 × ER-HoxA9_cells_Combo

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 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
Datasets on a similar topic

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