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Bone marrow failure, somatic rescue by p53 inactivation, and enhanced leukemogenesis in germline ERCC6L2 disease

GSE298958 Mus musculus (mouse) RNA-seq (gene expression) 48 samples Submitted 2026/05/15 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 48 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
48 samples: 16 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
Bone marrow failure, somatic rescue by p53 inactivation, and enhanced leukemogenesis in germ line ERCC6L2 diseaseBlood · 2026
Summary (written by the submitters)
Recessively inherited loss-of-function mutations in Excision Repair Cross-Complementing 6 like 2 (ERCC6L2) cause a bone marrow failure (BMF) syndrome characterized by moderate cytopenias, frequent somatic TP53 mutations, and a propensity to develop myeloid malignancies. The pathophysiology and molecular mechanisms underlying the BMF syndrome as well as its association with TP53-mutant clonal hematopoiesis (CH) and myeloid malignancies have remained poorly understood.
Read the full summary ↓
Using novel preclinical in vitro and in vivo model systems, we demonstrate that Ercc6l2 maintains the competitive fitness of hematopoietic stem and progenitor cells (HSPCs) by mitigating replication stress. Sustained replication stress and DNA damage in Ercc6l2-deficient HSPCs cause p53 pathway activation followed by cell cycle arrest and apoptosis. Moreover, Ercc6l2 deficiency results in decreased expression of master hematopoietic regulators Runx1 and Gata1 in HSPCs. Altogether, loss of Ercc6l2 leads to reduced HSPC numbers, bone marrow hypocellularity, and cytopenias. Notably, somatic Trp53 mutations restore cellular fitness of Ercc6l2-deficient HSPCs by abrogating p53 pathway activation and restoring Runx1 and Gata1 expression, thereby correcting the BMF phenotype. However, p53 loss fails to normalize replication stress, allowing for the accumulation of DNA damage over time which increases the likelihood for leukemic transformation. Our data uncover the pathogenesis of ERCC6L2 disease and provide a prototypic example of clonal compensation in BMF syndromes, where somatic mutations in leukemia-associated genes – in this case TP53 – transiently improve blood cell production at, however, the expense of increasing leukemogenic potential.
Published in
Bone marrow failure, somatic rescue by p53 inactivation, and enhanced leukemogenesis in germ line ERCC6L2 disease
Schimmer RR, Klemm N, Fullin J et al. · Blood 2026 · PMID 41490322 · doi:10.1182/blood.2025030230
This dataset
Open GSE298958 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 GSE298958_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 PRJNA1272001 and SRA study SRP589920. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41490322) ↗
Study design
16 conditions, mostly in triplicate
E6l2-KO HCD ×3 E6l2-KO DMSO ×3 E6l2-KO Etoposide ×3 wildtype HCD ×3 wildtype DMSO ×3 wildtype Etoposide ×3 Trp53-KO clone 4 Etoposide transformed ×3 Trp53-KO clone 6 Etoposide transformed ×3 +8 more

Supports a between-group comparison across 48 samples.

How we read this: 16 replicated groups read from 48 sample titles; they account for 48 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

+ 8 more — browse all 48 samples with per-sample file links →

Datasets on a similar topic

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