Identification of primary mediastinal B-cell lymphomas with higher clonal dominance and poorer outcome using 5' RACE.
Fiche publication
Date publication
septembre 2024
Journal
Blood advances
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MARTIN Laurent, Dr ROSSI Cédric
Tous les auteurs :
Camus V, Viennot M, Viailly PJ, Drieux F, Veresezan EL, Bobée V, Rainville V, Bohers E, Sesques P, Haioun C, Durot E, Bayaram M, Rossi C, Martin L, Penther D, Kaltenbach S, Bruneau J, Paillassa J, Tournilhac O, Gower N, Willaume A, Antier C, Renaud L, Leveque E, Decazes P, Becker S, Tonnelet D, Gaulard P, Tilly H, Molina T, Traverse-Glehen A, Donzel M, Ruminy P, Jardin F
Lien Pubmed
Résumé
Few data exist regarding the tumor B-cell receptor (BCR) repertoire and lymphoid microenvironment in primary mediastinal B-cell lymphoma (PMBL). We applied 5' rapid amplification of cDNA ends (5'RACE) to tumor RNA samples from 137 PMBL patients with available gene expression profiling and next-generation sequencing data. We obtained 5'RACE results for 75/137 (54.7%) patients, with clinical characteristics as follows: median [min-max] age, 33 [18-64] years; female, 53.3%; ECOG score 0-1, 86.7%; stage I-II, 57.3%; 1st-line treatment with anti-CD20 plus ACVBP, 72%; CHOP14, 14.7%; CHOP21, 13.3%. Among the 60 biopsies that expressed a productive BCR, we highlighted a strong somatic hypermutation profile with 58 (96.7%) patients carrying mutated IgVH, defined as <98% identity to the germline sequence. We then identified a subgroup of 12/75 patients (16%) with a worse prognosis (progression-free survival (PFS): HR [95% CI]=17 [3.2-88]; overall survival (OS): HR=21 [2.1-210]) associated with the highest clonal dominance status (HCD), defined by the dominant clonotype representing >81.1% and >78.6% of all CDR3 sequences for IgVH and IgVL, respectively. Compared to other patients, this subgroup had similar clinical characteristics but a greater median allele frequency for all somatic variants, decreased BCR diversity, and greater expression of PDL1/PDL2 and MS4A1 genes, suggesting a greater tumoral infiltration. According to a multivariate model integrating AID expression and BCR diversity, only HCD status was associated with outcome (PFS: HR=14.6 [2.46-86.8]; OS: HR=11.4 [1-128.8]). We confirmed this poorer prognosis in an independent cohort, in which 6/37 (16%) patients exhibited HCD (PFS: HR=12 [3-46]; OS: HR=17 [1.8-170]).
Référence
Blood Adv. 2024 09 18;: