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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.

Publication ,  Journal Article
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; Hsi, ED ...
Published in: Blood
November 2012

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.

Duke Scholars

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Published In

Blood

DOI

EISSN

1528-0020

ISSN

0006-4971

Publication Date

November 2012

Volume

120

Issue

19

Start / End Page

3986 / 3996

Related Subject Headings

  • Vincristine
  • Tumor Suppressor Protein p53
  • Treatment Outcome
  • Rituximab
  • Prognosis
  • Prednisone
  • Neoplasm Staging
  • Mutation, Missense
  • Mutation Rate
  • Mutation
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Xu-Monette, Z. Y., Wu, L., Visco, C., Tai, Y. C., Tzankov, A., Liu, W.-M., … 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
Xu-Monette, Zijun Y., Lin Wu, Carlo Visco, Yu Chuan Tai, Alexander Tzankov, Wei-min Liu, Santiago Montes-Moreno, et al. “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, no. 19 (November 2012): 3986–96. https://doi.org/10.1182/blood-2012-05-433334.
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. 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. 2012 Nov;120(19):3986–3996.

Published In

Blood

DOI

EISSN

1528-0020

ISSN

0006-4971

Publication Date

November 2012

Volume

120

Issue

19

Start / End Page

3986 / 3996

Related Subject Headings

  • Vincristine
  • Tumor Suppressor Protein p53
  • Treatment Outcome
  • Rituximab
  • Prognosis
  • Prednisone
  • Neoplasm Staging
  • Mutation, Missense
  • Mutation Rate
  • Mutation