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

Authors

Jianan Zheng, Yiman Peng, Xintong Deng, Lanxin Zhang, Zhongwang Wang, Xuelan Chen, He Li, Yanxin Li, Qi Zhang, Liuxian Zheng, Ziyi Qi, Lan Wang, Min Lu, Wenguo Cui, Li Wang, Yu Wu, Weili Zhao, Ting Niu, Chong Chen, Yu Liu

Published in

Nature communications. Jul 10, 2026. Epub Jul 10, 2026.

Abstract

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.

PMID:
42425977
Bibliographic data and abstract were imported from PubMed on 10 Jul 2026.

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