Histone Acetylation by HBO1 (KAT7) Activates Wnt/β-catenin Signaling to Promote Leukemogenesis in B-cell Acute Lymphoblastic Leukemia

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2023 Aug 4

PMID 37542030

Authors

Hao Wang

Yingqi Qiu

Honghao Zhang

Ning Chang

Yuxing Hu

Jianyu Chen

Rong Hu

Peiyun Liao

Zhongwei Li

Yulu Yang

Qingyan Cen

Xiangyang Ding

Meifang Li

Xiaoling Xie

Yuhua Li

Affiliations

Soon will be listed here.

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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