AUTHOR=Zhang Xuzhao , Wu Zhaoxing , Hao Yuanyuan , Yu Teng , Li Xian , Liang Yun , Li Jinfan , Huang Liansheng , Xu Yang , Li Xiuzhen , Xu Xiaohua , Wang Weiqin , Xu Genbo , Zhang Xiaohong , Lv Qinghua , Fang Yongming , Xu Rongzhen , Qian Wenbin 

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

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.888250

DOI=10.3389/fimmu.2022.888250

ISSN=1664-3224

ABSTRACT=Tumor protein 53 (TP53) mutation predicts 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 TP53 G/C to A/T mutation. Here we show that the frequency of this mutation was significantly higher in relapsed/refractory (R/R) as compared to non-R/R DLBCL, which was positively associated with APOBEC3B expression level. APOBEC3B overexpression induced 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.