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

Front Immunol. 2022 May 3:13:888250. doi: 10.3389/fimmu.2022.888250. eCollection 2022.


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.

Keywords: APOBEC3B; DLBCL; TP53 mutation; refractory; relapse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytidine Deaminase / metabolism
  • Humans
  • Lymphoma, Large B-Cell, Diffuse* / pathology
  • Minor Histocompatibility Antigens / genetics
  • Mutation
  • Prognosis
  • Tumor Suppressor Protein p53* / genetics
  • Tumor Suppressor Protein p53* / metabolism


  • Minor Histocompatibility Antigens
  • Tumor Suppressor Protein p53
  • APOBEC3B protein, human
  • Cytidine Deaminase