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

Zijun Y. Xu-Monette, Lin Wu, Carlo Visco, Yu Chuan Tai, Alexander Tzankov, Wei Min Liu, Santiago Montes-Moreno, Karen Dybkær, April Chiu, Attilio Orazi, Youli Zu, Govind Bhagat, Kristy L. Richards, Eric D. Hsi, X. Frank Zhao, William W L Choi, Xiaoying Zhao, J. Han Van Krieken, Qin Huang, Jooryung HuhWeiyun Ai, Maurilio Ponzoni, Andrés J M Ferreri, Fan Zhou, Brad S. Kahl, Jane N. Winter, Wei Xu, Jianyong Li, Ronald S. Go, Yong Li, Miguel A. Piris, Michael B. Møller, Roberto N. Miranda, Lynne V. Abruzzo, L. Jeffrey Medeiros, Ken H. Young

Research output: Contribution to journalArticle

Abstract

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 DNAbinding 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.

Original languageEnglish
Pages (from-to)3986-3996
Number of pages11
JournalBlood
Volume120
Issue number19
DOIs
Publication statusPublished - Nov 8 2012

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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    Xu-Monette, Z. Y., Wu, L., Visco, C., Tai, Y. C., Tzankov, A., Liu, W. M., Montes-Moreno, S., Dybkær, K., Chiu, A., Orazi, A., Zu, Y., Bhagat, G., Richards, K. L., Hsi, E. D., Zhao, X. F., Choi, W. W. L., Zhao, X., Van Krieken, J. H., Huang, Q., ... Young, K. H. (2012). 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. Blood, 120(19), 3986-3996. https://doi.org/10.1182/blood-2012-05-433334