GEO series

Inhibition of heme biosynthesis triggers cuproptosis in acute myeloid leukemia [RNA-Seq OCIAML3_ALAS1_KO_and_SA]

GSE303125 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2025/11/13 Platform GPL18573

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)
Samples: 12 samples: 3 × Vehicle vs 3 × SA vs 3 × sgSCR vs 3 × sgALAS1Groups 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: Inhibition of heme biosynthesis triggers cuproptosis in acute myeloid leukemiaCell · 2026

Summary (written by the submitters)

The ubiquitous metabolite heme has diverse enzymatic and signaling functions in most mammalian cells. Through integrated analyses of mouse models, human cell lines and primary patient samples, we identify de novo heme biosynthesis as a selective dependency in acute myeloid leukemia (AML). The dependency is underpinned by a propensity of AML cells, and especially leukemic stem cells (LSCs), to downregulate heme biosynthesis enzymes (HBEs) which promotes their self-renewal.

Read the full summary ↓

Inhibition of HBEs causes collapse of mitochondrial Complex IV (CIV) and dysregulates the copper-chaperone system inducing cuproptosis, a form of programmed cell death brought about by the oligomerization of lipoylated proteins by copper. Moreover, we identify pathways that are synthetic lethal with heme biosynthesis, including glycolysis, which can be leveraged for combination strategies. Altogether, our work uncovers a heme rheostat that controls gene expression and drug sensitivity in AML and implicates HBE inhibition as a novel cuproptosis trigger.

Published in

Inhibition of heme biosynthesis triggers cuproptosis in acute myeloid leukemia

Lewis AC, Gruber E, Franich R et al. · Cell 2026 · PMID 41265435 · doi:10.1016/j.cell.2025.10.028

This dataset

Open GSE303125 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 GSE303125_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 PRJNA1294202 and SRA study SRP602352. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41265435) ↗

Study design

3 × Vehicle vs 3 × SA vs 3 × sgSCR vs 3 × sgALAS1

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

GSM9118482 Vehicle rep1 Vehicle
GSM9118483 Vehicle rep2 Vehicle
GSM9118484 Vehicle rep3 Vehicle
GSM9118485 SA rep1 SA
GSM9118486 SA rep2 SA
GSM9118487 SA rep3 SA
GSM9118488 sgSCR rep1 sgSCR
GSM9118489 sgSCR rep2 sgSCR
GSM9118490 sgSCR rep3 sgSCR
GSM9118491 sgALAS1 rep1 sgALAS1
GSM9118492 sgALAS1 rep2 sgALAS1
GSM9118493 sgALAS1 rep3 sgALAS1

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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.