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

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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

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Lymphoma, Large B-Cell, Diffuse
Vincristine
Prednisone
Cyclophosphamide
Cells
Mutation
B-Lymphocytes
Germinal Center
Genes
Loss of Heterozygosity
Disease-Free Survival
Rituximab
Proteins
Survival
Therapeutics

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

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

In: Blood, Vol. 120, No. 19, 08.11.2012, p. 3986-3996.

Research output: Contribution to journalArticle

Xu-Monette, ZY, Wu, L, Visco, C, Tai, YC, Tzankov, A, Liu, WM, Montes-Moreno, S, Dybkær, 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 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, vol. 120, no. 19, pp. 3986-3996. https://doi.org/10.1182/blood-2012-05-433334
Xu-Monette, Zijun Y. ; Wu, Lin ; Visco, Carlo ; Tai, Yu Chuan ; Tzankov, Alexander ; Liu, Wei Min ; Montes-Moreno, Santiago ; Dybkær, Karen ; Chiu, April ; Orazi, Attilio ; Zu, Youli ; Bhagat, Govind ; Richards, Kristy L. ; Hsi, Eric D. ; Zhao, X. Frank ; Choi, William W L ; Zhao, Xiaoying ; Van Krieken, J. Han ; Huang, Qin ; Huh, Jooryung ; Ai, Weiyun ; Ponzoni, Maurilio ; Ferreri, Andrés J M ; Zhou, Fan ; Kahl, Brad S. ; Winter, Jane N. ; Xu, Wei ; Li, Jianyong ; Go, Ronald S. ; Li, Yong ; Piris, Miguel A. ; Møller, Michael B. ; Miranda, Roberto N. ; Abruzzo, Lynne V. ; Medeiros, L. Jeffrey ; Young, Ken H. / 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. In: Blood. 2012 ; Vol. 120, No. 19. pp. 3986-3996.
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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.",
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T1 - Mutational profile and prognostic significance of TP53 in diffuse large B-cell lymphoma patients treated with R-CHOP

T2 - Report from an International DLBCL Rituximab-CHOP Consortium Program Study

AU - Xu-Monette, Zijun Y.

AU - Wu, Lin

AU - Visco, Carlo

AU - Tai, Yu Chuan

AU - Tzankov, Alexander

AU - Liu, Wei Min

AU - Montes-Moreno, Santiago

AU - Dybkær, Karen

AU - Chiu, April

AU - Orazi, Attilio

AU - Zu, Youli

AU - Bhagat, Govind

AU - Richards, Kristy L.

AU - Hsi, Eric D.

AU - Zhao, X. Frank

AU - Choi, William W L

AU - Zhao, Xiaoying

AU - Van Krieken, J. Han

AU - Huang, Qin

AU - Huh, Jooryung

AU - Ai, Weiyun

AU - Ponzoni, Maurilio

AU - Ferreri, Andrés J M

AU - Zhou, Fan

AU - Kahl, Brad S.

AU - Winter, Jane N.

AU - Xu, Wei

AU - Li, Jianyong

AU - Go, Ronald S.

AU - Li, Yong

AU - Piris, Miguel A.

AU - Møller, Michael B.

AU - Miranda, Roberto N.

AU - Abruzzo, Lynne V.

AU - Medeiros, L. Jeffrey

AU - Young, Ken H.

PY - 2012/11/8

Y1 - 2012/11/8

N2 - 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.

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