Aberrantly Activated APOBEC3B Is Associated With Mutant p53-Driven Refractory/Relapsed Diffuse Large B-Cell Lymphoma

作者：Xuzhao Zhang, Xuzhao Zhang, Zhaoxing Wu, Yuanyuan Hao, Teng Yu, Xian Li, Yun Liang, Jinfan Li, Liansheng Huang, Yang Xu, Xiuzhen Li, Xiaohua Xu, Weiqin Wang, Gen-bo Xu, Xiaohong Zhang, Xiaohong Zhang, Qinghua Lv, Yongming Fang, Rongzhen Xu, Wenbin Qian · 发表于：Frontiers in Immunology · 年份：2022 · DOI：10.3389/fimmu.2022.888250 · 被引用次数：11 · 研究领域：Lymphoma Diagnosis and Treatment、CNS Lymphoma Diagnosis and Treatment、Viral-associated cancers and disorders

Tumor protein 53 ( TP53 ) mutation predicts an unfavorable prognosis in diffuse large B-cell lymphoma (DLBCL), but the molecular basis for this association remains unclear. In several malignancies, the cytidine deaminase apolipoprotein B mRNA editing enzyme catalytic subunit 3B (APOBEC3B) has been reported to be associated with the TP53 G/C-to-A/T mutation. Here, we show that the frequency of this mutation was significantly higher in relapsed/refractory (R/R) than in non-R/R DLBCL, which was positively associated with the APOBEC3B expression level. APOBEC3B overexpression induced the TP53 G/C-to-A/T mutation in vitro , resulting in a phenotype similar to that of DLBCL specimens. Additionally, APOBEC3B-induced p53 mutants promoted the growth of DLBCL cells and enhanced drug resistance. These results suggest that APOBEC3B is a critical factor in mutant p53-driven R/R DLBCL and is therefore a potential therapeutic target.