期刊
BLOOD
卷 120, 期 19, 页码 3986-3996出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2012-05-433334
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资金
- Shannon Timmins Leukemia Fellowship Award at The University of Texas MD Anderson Cancer Center
- Stiftung zur Krebsbekaempfung Zurich Grant [269]
- University of Texas MD Anderson Cancer Center Institutional Research and Development Fund
- University of Texas MD Anderson Cancer Center Institutional Research Grant Award
- MD Anderson Cancer Center SPORE Research Development Program Award
- Gundersen Lutheran Medical Foundation Award
- MD Anderson Cancer Center Collaborative Funds
- Roche
- HTG Molecular
- Daiichi Sankyo
- Forward Lymphoma Fund
- National Cancer Institute/National Institutes of Health [R01CA138688, 1RC1CA146299, P50CA142509]
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)
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