TY - JOUR
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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84868602463&partnerID=8YFLogxK
U2 - 10.1182/blood-2012-05-433334
DO - 10.1182/blood-2012-05-433334
M3 - Article
C2 - 22955915
AN - SCOPUS:84868602463
SN - 0006-4971
VL - 120
SP - 3986
EP - 3996
JO - Blood
JF - Blood
IS - 19
ER -