Mutational profile and prognostic significance of TP53 in diffuse large B-cell lymphoma patients treated with R-CHOP: report from an International DLBCL Rituximab-CHOP Consortium Program Study.

Published

Journal Article

TP53 mutation is an independent marker of poor prognosis in patients with diffuse large B-cell lymphoma (DLBCL) treated with cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (CHOP) therapy. However, its prognostic value in the rituximab immunochemotherapy era remains undefined. In the present study of a large cohort of DLBCL patients treated with rituximab plus CHOP (R-CHOP), we show that those with TP53 mutations had worse overall and progression-free survival compared with those without. Unlike earlier studies of patients treated with CHOP, TP53 mutation has predictive value for R-CHOP-treated patients with either the germinal center B-cell or activated B-cell DLBCL subtypes. Furthermore, we identified the loop-sheet-helix and L3 motifs in the DNA-binding domain to be the most critical structures for maintaining p53 function. In contrast, TP53 deletion and loss of heterozygosity did not confer worse survival. If gene mutation data are not available, immunohistochemical analysis showing > 50% cells expressing p53 protein is a useful surrogate and was able to stratify patients with significantly different prognoses. We conclude that assessment of TP53 mutation status is important for stratifying R-CHOP-treated patients into distinct prognostic subsets and has significant value in the design of future therapeutic strategies.

Full Text

Duke Authors

Cited Authors

  • Xu-Monette, ZY; Wu, L; Visco, C; Tai, YC; Tzankov, A; Liu, W-M; Montes-Moreno, S; Dybkaer, K; Chiu, A; Orazi, A; Zu, Y; Bhagat, G; Richards, KL; Hsi, ED; Zhao, XF; Choi, WWL; Zhao, X; van Krieken, JH; Huang, Q; Huh, J; Ai, W; Ponzoni, M; Ferreri, AJM; Zhou, F; Kahl, BS; Winter, JN; Xu, W; Li, J; Go, RS; Li, Y; Piris, MA; Møller, MB; Miranda, RN; Abruzzo, LV; Medeiros, LJ; Young, KH

Published Date

  • November 2012

Published In

Volume / Issue

  • 120 / 19

Start / End Page

  • 3986 - 3996

PubMed ID

  • 22955915

Pubmed Central ID

  • 22955915

Electronic International Standard Serial Number (EISSN)

  • 1528-0020

International Standard Serial Number (ISSN)

  • 0006-4971

Digital Object Identifier (DOI)

  • 10.1182/blood-2012-05-433334

Language

  • eng