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Depletion of ribosome biogenesis factors in NPM1-mutant acute myeloid leukemia: Insights into direct consequences of the mutation and implications for treatment

GSE264084 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2025/09/01 Platform GPL11154
At a glance

RNA-seq (gene expression) · human · 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
Homo sapiens (human)
Topic
Acute myeloid leukemiaThis series is part of our curated briefing on it.
Samples
12 samples: 3 × OCI-AML2, gControl, vs 3 × OCI-AML2, gTsr3, vs 3 × OCI-AML3, gControl, vs 3 × OCI-AML3, gTSR3,Groups 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
Posttranscriptional depletion of ribosome biogenesis factors engenders therapeutic vulnerabilities in NPM1-mutant AMLBlood · 2025
Summary (written by the submitters)
Mutations in the NPM1 gene are found in more than 30% of acute myeloid leukemia (AML) cases. The mutations disrupt a nucleolar localization signal (NoLS) and create a novel nuclear export signal (NES), leading to cytoplasmic displacement of the protein (NPM1c). NPM1c mutations prime hematopoietic progenitors to leukemic transformation, but their precise molecular consequences remain elusive.
Read the full summary ↓
Here, we first examined the effects of isolated NPM1c mutations on the global proteome of pre-leukemic hematopoietic progenitors using a conditional knock-in Npm1cA/+ mouse model. We discovered a significant depletion of many factors involved in the ribosome biogenesis pathway which, importantly, persists in NPM1-mutant AML patients. Next, we found that pre-leukemic Npm1cA/+ cells display higher sensitivity to Actinomycin D (ActD) and other RNA pol I inhibitors when compared to wild-type Npm1+/+ cells. Combination treatment with ActD and Venetoclax inhibited the growth and colony forming ability of pre-leukemic and leukemic NPM1c+ cells and low-dose ActD treatment was able to re-sensitize resistant NPM1c+ cells to Venetoclax. Finally, by contrasting our findings with data from CRISPR drop-out screens, we identified and validated TSR3, a ribosome maturation factor of the 40S ribosomal subunit whose knock-out preferentially inhibited the proliferation of NPM1c+ AML cells by activating a p53-dependent response. Similar to low-dose ActD treatment, TSR3 depletion could partially restore sensitivity to Venetoclax in therapy-resistant NPM1c+ AML models.
Published in
Posttranscriptional depletion of ribosome biogenesis factors engenders therapeutic vulnerabilities in NPM1-mutant AML
Damaskou A, Wilson R, Gozdecka M et al. · Blood 2025 · PMID 40561247 · doi:10.1182/blood.2024026113
This dataset
Open GSE264084 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 GSE264084_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 PRJNA1100960 and SRA study SRP502173. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40561247) ↗
Study design
3 × OCI-AML2, gControl, vs 3 × OCI-AML2, gTsr3, vs 3 × OCI-AML3, gControl, vs 3 × OCI-AML3, gTSR3,

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
More Acute myeloid leukemia datasets

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