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

被引：313

作者：

Xu-Monette, Zijun Y. ^{[1
]}

Wu, Lin ^{[2
]}

Visco, Carlo ^{[3
]}

Tai, Yu Chuan ^{[2
]}

Tzankov, Alexander ^{[4
]}

Liu, Wei-min ^{[2
]}

Montes-Moreno, Santiago ^{[5
]}

Dybkaer, Karen ^{[6
]}

Chiu, April ^{[7
]}

Orazi, Attilio ^{[8
]}

Zu, Youli ^{[9
]}

Bhagat, Govind ^{[10
,11
]}

Richards, Kristy L. ^{[12
]}

Hsi, Eric D. ^{[13
]}

Zhao, X. Frank ^{[14
]}

Choi, William W. L. ^{[15
]}

Zhao, Xiaoying ^{[16
]}

van Krieken, J. Han ^{[17
]}

Huang, Qin ^{[18
]}

Huh, Jooryung ^{[19
]}

Ai, Weiyun ^{[20
]}

Ponzoni, Maurilio ^{[21
]}

Ferreri, Andres J. M. ^{[21
]}

Zhou, Fan ^{[22
]}

Kahl, Brad S. ^{[23
]}

Winter, Jane N. ^{[24
]}

Xu, Wei ^{[25
]}

Li, Jianyong ^{[25
]}

Go, Ronald S. ^{[26
]}

Li, Yong ^{[27
]}

Piris, Miguel A. ^{[5
]}

Moller, Michael B. ^{[28
]}

Miranda, Roberto N. ^{[1
]}

Abruzzo, Lynne V. ^{[1
]}

Medeiros, L. Jeffrey ^{[1
]}

Young, Ken H. ^{[1
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA

[2] Roche Mol Syst Inc, Pleasanton, CA USA

[3] San Bortolo Hosp, Vicenza, Italy

[4] Univ Basel Hosp, CH-4031 Basel, Switzerland

[5] Hosp Univ Marques Valdecilla, Santander, Spain

[6] Aarhus Univ Hosp, Aalborg Hosp, Aalborg, Denmark

[7] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA

[8] Cornell Univ, Weill Med Coll, New York, NY 10021 USA

[9] Methodist Hosp, Houston, TX 77030 USA

[10] Columbia Univ, Med Ctr, New York, NY USA

[11] New York Presbyterian Hosp, New York, NY USA

[12] Univ N Carolina, Sch Med, Chapel Hill, NC USA

[13] Cleveland Clin, Cleveland, OH 44106 USA

[14] Univ Maryland, Sch Med, Baltimore, MD 21201 USA

[15] Univ Hong Kong Li Ka Shing, Fac Med, Hong Kong, Hong Kong, Peoples R China

[16] Zhejiang Univ, Sch Med, Univ Hosp 2, Hangzhou 310003, Zhejiang, Peoples R China

[17] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands

[18] City Hope Natl Med Ctr, Duarte, CA 91010 USA

[19] Univ Ulsan, Coll Med, Asan Med Ctr, Seoul, South Korea

[20] Univ Calif San Francisco, Sch Med, San Francisco, CA USA

[21] Ist Sci San Raffaele, Milan, Italy

[22] SW Washington Med Ctr, Vancouver, WA USA

[23] Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA

[24] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA

[25] Nanjing Med Univ, Affiliated Hosp 1, Jiangsu Prov Hosp, Nanjing, Jiangsu, Peoples R China

[26] Gundersen Lutheran Hlth Syst, La Crosse, WI USA

[27] Univ Louisville, Louisville, KY 40292 USA

[28] Odense Univ Hosp, DK-5000 Odense, Denmark

来源：

BLOOD | 2012年 / 120卷 / 19期

基金：

美国国家卫生研究院;

关键词：

ARF TUMOR-SUPPRESSOR; P53; GENE-MUTATIONS; RESPONSE CRITERIA; POOR SURVIVAL; CHEMOTHERAPY; EXPRESSION; LEUKEMIA; CALCIUM; MECHANISM; APOPTOSIS;

D O I：

10.1182/blood-2012-05-433334

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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. (Blood. 2012;120(19):3986-3996)

引用

页码：3986 / 3996

页数：11

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