B-细胞急性淋巴细胞白血病（B-ALL）是一种预后不良的侵袭性血液疾病。组蛋白乙酰化的失调在B-ALL的发病和进展中具有重要意义。作为一种基础乙酰转移酶基因，HBO1（赖氨酸乙酰转移酶7/KAT7）在B-ALL中的作用尚未得到研究。在这项研究中，我们发现HBO1在人类B-ALL细胞中的表达升高，并与无病生存率差相关。令人惊讶的是，HBO1敲除抑制了B-ALL细胞的存活能力、增殖和G1-S周期进程，同时引发细胞凋亡。相反，HBO1的过表达增强了细胞的存活能力和增殖，但抑制了凋亡的激活。体内实验的结果也证实了HBO1敲除对肿瘤生长的抑制作用。在机制上，HBO1乙酰化了组蛋白H3K14、H4K8和H4K12，从而上调CTNNB1的表达，进而激活Wnt/β-连环蛋白信号通路。此外，一种新型HBO1小分子抑制剂WM-3835有效抑制了B-ALL的进展。我们的数据将HBO1识别为B-ALL中CTNNB1的一种有效调节器，具有治疗潜力。© 2023. 作者。

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.© 2023. The Author(s).