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The histone-methyltransferase DOT1L cooperates with LSD1 to control cell division in blast-phase MPN [RNA-seq]

GSE300512 Homo sapiens (human) RNA-seq (gene expression) 23 samples Submitted 2025/07/29 Platform GPL34284
At a glance

RNA-seq (gene expression) · human · 23 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)
Samples
23 samples: 8 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
The histone-methyltransferase DOT1L cooperates with LSD1 to control cell division in blast-phase MPNLeukemia · 2025
Summary (written by the submitters)
Persistence of JAK2-mutated clones that may undergo clonal evolution and malignant transformation remains a challenge in myeloproliferative neoplasms (MPN), Novel therapeutic approaches to attenuate clonal evolution and progression to blast-phase are therefore urgently needed. LSD1 (KDM1A) inhibitors reduce symptoms and clonal burden in MPN, but whether these compounds may be effective in advanced disease stages remained so far elusive.
Read the full summary ↓
Using a chromatin-focused CRISPR-Cas9 screen, we identified the histone methyltransferase DOT1L as a synthetic lethal target under pharmacologic LSD1 inhibition. DOT1L knockout impaired cellular fitness, reduced proliferation, and prolonged survival in xenografts. Furthermore, genetic inactivation of DOT1L increased LSD1 inhibitor sensitivity up to 100-fold resulting in cell cycle arrest and apoptosis induction in TP53 mutant blast-phase MPN. Mechanistically, we have identified a novel, non-canonical function of DOT1L which co-occupied LSD1-bound enhancers and contributed to the repression of transcriptional programs independent of its enzymatic activity. DOT1L loss cooperated with LSD1 inhibitors to activate tumor suppressive programs, while pharmacologic inhibition of DOT1Ls catalytic activity failed to elicit comparable effects. These findings indicate that leveraging DOT1L targeting via protein degradation or RNA interference, rather than conventional enzymatic inhibition, could enhance the therapeutic efficacy of LSD1 inhibitors in blast-phase MPN.
Published in
The histone-methyltransferase DOT1L cooperates with LSD1 to control cell division in blast-phase MPN
Kapahnke K, Plenge T, Klaus T et al. · Leukemia 2025 · PMID 40781484 · doi:10.1038/s41375-025-02719-y
This dataset
Open GSE300512 in finder → Find more human 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 GSE300512_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 PRJNA1281080 and SRA study SRP593922. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40781484) ↗
Study design
8 conditions, mostly in triplicate
HEL_DOT1L-ko_Bomedemstat_5d ×3 HEL_DOT1L-ko_Bomedemstat_24h ×3 HEL_NTC_DMSO ×3 HEL_NTC_Bomedemstat_5d ×3 HEL_NTC_Bomedemstat_24h ×3 MPN-BP_patient_DOT1L-shRNA ×3 MPN-BP_patient_SCR-shRNA ×3 HEL_DOT1L-ko_DMSO ×2

Supports a case/control comparison: 6 samples read as cases, 5 as controls.

How we read this: 8 replicated groups read from 23 sample titles; they account for 23 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
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