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AS1842856: A dual FOXO1-GSK3 inhibitor for targeting B-ALL-specific molecular vulnerabilities

GSE283254 Mus musculus (mouse) RNA-seq (gene expression) 24 samples Submitted 2025/07/23 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 24 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
24 samples: 24 samples, each with a distinct title — no replicated groupsGroups 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
Beyond FOXO1: AS1842856 inhibits GSK3 to enhance cytotoxic effects in B-ALLBlood advances · 2025
Summary (written by the submitters)
Activation of the transcription factor FOXO1 contributes to multiple pathological processes. The FOXO1 inhibitor AS1842856 demonstrated strong therapeutic effects in pre-clinical models of common diseases like diabetes and anthracyclines-induced heart failure. We have previously identified FOXO1 as a B-ALL dependency and demonstrated in in vivo B-ALL models that AS1842856 increased the survival and decreased B-ALL tumor load in all critical organ compartments, but most efficiently in the CNS.
Read the full summary ↓
Here, we interrogated the underlying molecular mechanisms by comparison of the transcriptomic effects of AS1842856 and Foxo1-KO in a B-ALL mouse model. Despite the significant similarity in sets of regulated genes, we identified GSK3B inhibition as a signature enriched only in AS1842856-treated cells. Using an in vitro kinase assay, we identified AS1842856 as a direct GSK3B inhibitor that ultimately stabilizes CTNNB1. CTNNB1-KO partially protected B-ALL cell lines from the cytotoxic effect of AS1842856. At the same time, using a chemical protein degradation model, we found that FOXO1 indeed contributes to the cytotoxic effect of AS1842856. We conclude that AS1842856 targets two known B-ALL vulnerabilities: GSK3B and FOXO1. The unique mode of action, low toxicity, and ability to penetrate the blood-brain barrier warrant further investigation of the therapeutic potential of AS1842856 in B-ALL.
Published in
Beyond FOXO1: AS1842856 inhibits GSK3 to enhance cytotoxic effects in B-ALL
Ketzer F, Büttner U, Geist D et al. · Blood advances 2025 · PMID 40638129 · doi:10.1182/bloodadvances.2024015560
This dataset
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.

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 GSE283254_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA1191823 and SRA study SRP548203. Searching any of these in the dataset finder brings you back here.

Study design
24 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 24 sample titles: 24 distinct titles with little repetition. 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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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.