1. Aberrantly Activated APOBEC3B Is Associated With Mutant p53-Driven Refractory/Relapsed Diffuse Large B-Cell Lymphoma
- Author
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Xuzhao Zhang, Zhaoxing Wu, Yuanyuan Hao, Teng Yu, Xian Li, Yun Liang, Jinfan Li, Liansheng Huang, Yang Xu, Xiuzhen Li, Xiaohua Xu, Weiqin Wang, Genbo Xu, Xiaohong Zhang, Qinghua Lv, Yongming Fang, Rongzhen Xu, and Wenbin Qian
- Subjects
TP53 mutation ,APOBEC3B ,DLBCL ,refractory ,relapse ,Immunologic diseases. Allergy ,RC581-607 - Abstract
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.
- Published
- 2022
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