Mutational profile and prognostic significance of TP53 in diffuse large B-cell lymphoma patients treated with rituximab-CHOP: a report from an International DLBCL Rituximab-CHOP Consortium Program study
Menée sur 506 patients atteints d'un lymphome diffus à grandes cellules B traité à l'aide du protocole de chimiothérapie R-CHOP, cette étude évalue l'association entre la présence de mutations du gène TP53 et la survie des patients
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 (R) immuno-chemotherapy era remains undefined. In this large cohort of DLBCL patients treated with R-CHOP, we show that those with TP53 mutations had worse overall and progression-free survival compared to 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 (GCB)- and activated B-cell (ABC)-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 was 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 , résumé, 2012