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

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Zijun Y Xu-Monette
  • ,
  • Lin Wu
  • ,
  • Carlo Visco
  • ,
  • Yu Chuan Tai
  • ,
  • Alexander Tzankov
  • ,
  • Wei-Min Liu
  • ,
  • Santiago Montes-Moreno
  • ,
  • Karen Dybkær, Denmark
  • April Chiu
  • ,
  • Attilio Orazi
  • ,
  • Youli Zu
  • ,
  • Govind Bhagat
  • ,
  • Kristy L Richards
  • ,
  • Eric D Hsi
  • ,
  • X Frank Zhao
  • ,
  • William Wl Choi
  • ,
  • Xiaoying Zhao
  • ,
  • J Han van Krieken
  • ,
  • Qin Huang
  • ,
  • Jooryung Huh
  • ,
  • Weiyun Ai
  • ,
  • Maurilio A Ponzoni
  • ,
  • Andres Jm 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
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 (R) immuno-chemotherapy era remains undefined. In this large cohort of DLBCL patients treated with R-CHOP, we show that those with TP53 mutations had worse overall and progression-free survival compared to 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 (GCB)- and activated B-cell (ABC)-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 was 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
JournalBlood
Volume120
Issue19
Pages (from-to)3986-3996
Number of pages11
ISSN0006-4971
DOIs
Publication statusPublished - 2012

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