GEO series

Intracellular iron homeostasis-regulated epigenetic reprogramming contributes to -7/del(7q) leukemia

GSE294258 Mus musculus Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing 71 samples Submitted 2026/04/21 Platform GPL24247Platform GPL34328Platform GPL33944

Summary

Chromosome copy number variations are poorly understood drivers of human malignancies. -7/del(7q) is common in acute myeloid leukemia, confers a poor prognosis, and is thought to harbor several tumor suppressors. Previously, we identified the histone methyltransferase KMT2C as a tumor suppressor in this region. Here, through a differentiation CRISPR screen in hematopoietic stem and progenitor cells, we find that the mitochondrial iron transporter ABCB8 is essential for their differentiation. ABCB8 deficiency accelerates leukemogenesis in vivo and disrupts iron homeostasis, reducing cytoplasmic iron availability and impairing iron-dependent enzymes, including the histone demethylase KDM6A. Consequently, ABCB8 loss elevates H3K27me3 levels, repressing differentiation genes in an iron- and KDM6A-dependent manner. Notably, ABCB8 and KMT2C, neighboring genes on 7q, cooperatively regulate H3K27me3 to suppress leukemogenesis. Our findings reveal ABCB8 as a tumor suppressor in -7/del(7q) acute myeloid leukemia and uncover an epigenetic collaboration between neighboring tumor suppressors, driven by iron-mediated chromatin remodeling.

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Direct links to NCBI, no account and no request form: the whole study as GSE294258_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 71 samples. Raw sequencing reads are also available from ENA.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗ Raw reads on ENA ↗

Also filed as BioProject PRJNA1248888 and SRA study SRP577711. Searching any of these in the dataset finder brings you back here.

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Study design

36 conditions, each sampled once — no replicated groups

mouse HSPCs with shRen rep1, ×2 mouse HSPCs with shRen rep2, ×2 mouse HSPCs with shRen rep3, ×2 H3K27me3 CUT&Tag Seq of mouse HSPCs with shRen ×2

Supports a case/control comparison: 5 samples read as cases, 3 as controls.

Read from the first 40 of 71 sample titles: 36 distinct titles with little repetition. Check it against the sample list below before relying on it.

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