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

被引：5

作者：

Zhang, Xuzhao ^{[1
,2
,3
]}

Wu, Zhaoxing ^{[1
]}

Hao, Yuanyuan ^{[1
]}

Yu, Teng ^{[1
]}

Li, Xian ^{[1
]}

Liang, Yun ^{[1
]}

Li, Jinfan ^{[4
]}

Huang, Liansheng ^{[1
]}

Xu, Yang ^{[1
]}

Li, Xiuzhen ^{[4
]}

Xu, Xiaohua ^{[1
]}

Wang, Weiqin ^{[1
]}

Xu, Genbo ^{[1
]}

Zhang, Xiaohong ^{[1
]}

Lv, Qinghua ^{[2
]}

Fang, Yongming ^{[2
]}

Xu, Rongzhen ^{[1
,2
]}

Qian, Wenbin ^{[1
]}

机构：

[1] Zhejiang Univ, Dept Hematol, Affiliated Hosp 2, Sch Med, Hangzhou, Peoples R China

[2] Zhejiang Univ, Canc Inst, Key Lab Canc Prevent & Intervent, China Natl Minist Educ,Affiliated Hosp 2,Sch Med, Hangzhou, Peoples R China

[3] Zhejiang Univ, Zhejiang Prov Key Lab Canc Mol Cell Biol, Hangzhou, Peoples R China

[4] Zhejiang Univ, Sch Med, Dept Pathol, Affiliated Hosp 2, Hangzhou, Peoples R China

来源：

FRONTIERS IN IMMUNOLOGY | 2022年 / 13卷

基金：

中国国家自然科学基金;

关键词：

TP53; mutation; APOBEC3B; DLBCL; refractory; relapse; CYTIDINE DEAMINASES; P53; MUTATIONS; TP53; GENE; DNA; VIRUS; EXPRESSION; CHEMOTHERAPY; MUTAGENESIS; SURVIVAL; RISK;

D O I：

10.3389/fimmu.2022.888250

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页数：13

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