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

  • Commun Biol. 2026 Jun 1. doi: 10.1038/s42003-026-10399-2.
Yin Ye  #  1 ,  Yueying Zhang  #  1 ,  Tingting Wang  #  1 ,  Meimei Dongye  2 ,  Xiaohui Chen  1 ,  Rongtao Xue  3 ,  Shunqing Wang  4 ,  Jianling Yang  5 ,  Lixiang Xue  5 ,  Zhibin Huang  6 ,  Fei Dong  7 ,  Wenqing Zhang  8 ,  Wei Liu  9
Affiliations
  • 1. The Innovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of Technology, Guangzhou, China.
  • 2. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
  • 3. Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • 4. Department of Hematology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
  • 5. Department of Radiation Oncology, Peking University Third Hospital Cancer Center, Peking University Third Hospital, Beijing, China.
  • 6. The Innovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of Technology, Guangzhou, China. [email protected].
  • 7. Department of Hematology, Lymphoma Research Center, Peking University Third Hospital, Beijing, China. [email protected].
  • 8. The Innovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of Technology, Guangzhou, China. [email protected].
  • 9. The Innovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of Technology, Guangzhou, China. [email protected].
  • # Contributed equally.
PMID: 42225948 DOI: 10.1038/s42003-026-10399-2
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.

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