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CBX4 enhances acute monocytic leukemia development via HDAC-mediated suppression of Runx1.

Created on 02 Jun 2026

Authors

Yin Ye, Yueying Zhang, Tingting Wang, Meimei Dongye, Xiaohui Chen, Rongtao Xue, Shunqing Wang, Jianling Yang, Lixiang Xue, Zhibin Huang, Fei Dong, Wenqing Zhang, Wei Liu

Published in

Communications biology. Jun 01, 2026. Epub Jun 01, 2026.

Abstract

Acute monocytic leukemia (AML-M5) is a type of acute myeloid leukemia, characterized by a dominance of monocytes in the bone marrow and peripheral blood. AML-M5 exhibits a poor prognosis compared to other AML subtypes. Despite clinical recognition, current research on AML-M5 remains relatively limited, and its underlying pathogenic mechanisms are not yet fully understood. In this study, we uncover a distinct and heightened expression of CBX4, a core component of PRC1, in the peripheral blood of individuals diagnosed with AML-M5. By generating cbx4 overexpression transgenic and deleted mutant zebrafish lines, we observe elevated cbx4 expression in monocyte/macrophage, selectively modulating their production during zebrafish hematopoiesis. Notably, aging zebrafish with cbx4 overexpression exhibit a progression to AML-M5-like hematopoiesis. Further mechanistic analyses reveal that Cbx4 regulates the fate of monocyte/macrophage lineage by suppressing runx1 expression. This suppression is achieved through the recruitment of HDAC to the runx1 promoter via cbx4, resulting in the down-regulation of the H3K27 acetylation level of runx1. These findings offer novel insights, providing potential avenues for risk assessment and molecular diagnosis of AML-M5 leukemia. Moreover, CBX4 emerges as a promising target for the diagnosis and treatment of AML-M5 leukemia.

PMID:
42225948
Bibliographic data and abstract were imported from PubMed on 02 Jun 2026.

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