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A novel potent and selective GCN2 inhibitor, APL-4098, has anti-leukemic activity through dysregulation of mitochondrial function

GSE319868 Homo sapiens (human) RNA-seq (gene expression) 64 samples Submitted 2026/02/18 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 64 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
64 samples: 64 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
A Novel Potent and Selective GCN2 Inhibitor, APL-4098, Has Antileukemic Activity through Dysregulation of Mitochondrial FunctionClinical cancer research : an official journal of the American Association for Cancer Research · 2026
Summary (written by the submitters)
Purpose: GCN2, one of the four kinases that activate the Integrated Stress Response to maintain proteostasis, has been shown to support cancer cell growth and survival in multiple preclinical cancer models. Acute myeloid leukemia (AML) is an aggressive hematological malignancy with dismal prognosis and high relapse rates that is marked by a dependency on finely tuned proteostasis.
Read the full summary ↓
Here, we investigate the anti-leukemic potential of a new small-molecule GCN2 inhibitor, APL-4098. Experimental design: selectivity and potency of APL-4098 were assessed using biochemical and cell-based assays. Anti-leukemic effects were evaluated ex vivo in primary patient-derived AML and in vivo using cell line-derived (CDX) and patient-derived (PDX) xenograft models. Synergy of APL-4098 and venetoclax was examined in the PDX. RNA sequencing and metabolic assays were used to explore APL-4098 mechanism of action. Results: APL-4098 exhibited nanomolar-range potency against and high selectivity for GCN2. APL-4098 showed strong anti-proliferative activity ex vivo across two independent cohorts of primary AML patient cells, including cytotoxic effects on the leukemia stem cells (LSCs) and in vivo, achieving 98% tumor growth inhibition in an AML CDX. In a PDX, APL-4098 preferentially depleted the LSC-enriched compartment and, in combination with venetoclax, reduced leukemia burden by over 98%. Transcriptomic and metabolic analyses revealed APL-4098 compromises mitochondrial function and elicits the mitochondrial unfolded protein response. Conclusions: APL-4098 is a novel, potent and selective GCN2 inhibitor with strong preclinical efficacy against AML cells, including LSCs. Our findings support APL-4098 as a promising candidate for AML treatment.
Published in
A Novel Potent and Selective GCN2 Inhibitor, APL-4098, Has Antileukemic Activity through Dysregulation of Mitochondrial Function
Román-Trufero M, Whitlock G, Seydoux C et al. · Clinical cancer research : an official journal of the American Association for Cancer Research 2026 · PMID 41729725 · doi:10.1158/1078-0432.CCR-25-1444
This dataset
Open GSE319868 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 GSE319868_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 PRJNA1425440. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41729725) ↗
Study design
64 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 64 sample titles: 64 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

+ 24 more — browse all 64 samples with per-sample file links →

More Acute myeloid leukemia datasets

Search all human RNA-seq datasets in GEO →

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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.