2. Academic Validation
  3. Histone acetylation by HBO1 (KAT7) activates Wnt/β-catenin signaling to promote leukemogenesis in B-cell acute lymphoblastic leukemia

Histone acetylation by HBO1 (KAT7) activates Wnt/β-catenin signaling to promote leukemogenesis in B-cell acute lymphoblastic leukemia

  • Cell Death Dis. 2023 Aug 4;14(8):498. doi: 10.1038/s41419-023-06019-0.
Hao Wang # 1,  Yingqi Qiu # 1,  Honghao Zhang # 2,  Ning Chang 1,  Yuxing Hu 1,  Jianyu Chen 1,  Rong Hu 1,  Peiyun Liao 1,  Zhongwei Li 1,  Yulu Yang 1,  Qingyan Cen 1,  Xiangyang Ding 1,  Meifang Li 1,  Xiaoling Xie 3,  Yuhua Li 4 5
Affiliations

Affiliations

  • 1 Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, P. R. China.
  • 2 Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, P. R. China. Fortunezhh@163.com.
  • 3 Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, P. R. China. xx1413@smu.edu.cn.
  • 4 Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, P. R. China. liyuhua1974@outlook.com.
  • 5 Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, Guangdong, 510005, P. R. China. liyuhua1974@outlook.com.
  • # Contributed equally.
PMID: 37542030 DOI: 10.1038/s41419-023-06019-0
Abstract

B-cell acute lymphoblastic leukemia (B-ALL) is an aggressive hematological disorder with a dismal prognosis. The dysregulation of histone acetylation is of great significance in the pathogenesis and progression of B-ALL. Regarded as a fundamental acetyltransferase gene, the role of HBO1 (lysine acetyltransferase 7/KAT7) in B-ALL has not been investigated. Herein, we found that HBO1 expression was elevated in human B-ALL cells and associated with poor disease-free survival. Strikingly, HBO1 knockdown inhibited viability, proliferation, and G1-S cycle progression in B-ALL cells, while provoking Apoptosis. In contrast, ectopic overexpression of HBO1 enhanced cell viability and proliferation but inhibited apoptotic activation. The results of in vivo experiments also certificated the inhibitory effect of HBO1 knockdown on tumor growth. Mechanistically, HBO1 acetylated histone H3K14, H4K8, and H4K12, followed by upregulating CTNNB1 expression, resulting in activation of the Wnt/β-catenin signaling pathway. Moreover, a novel small molecule inhibitor of HBO1, WM-3835, potently inhibited the progression of B-ALL. Our data identified HBO1 as an efficacious regulator of CTNNB1 with therapeutic potential in B-ALL.

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