Frontiers in Immunology (May 2022)

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

  • Xuzhao Zhang,
  • 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,
  • Genbo Xu,
  • Xiaohong Zhang,
  • Qinghua Lv,
  • Yongming Fang,
  • Rongzhen Xu,
  • Rongzhen Xu,
  • Wenbin Qian

DOI
https://doi.org/10.3389/fimmu.2022.888250
Journal volume & issue
Vol. 13

Abstract

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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.

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