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Identification of primary mediastinal B-cell lymphomas with higher clonal dominance and poorer outcome using 5' RACE.
Camus, Vincent; Viennot, Mathieu; Viailly, Pierre-Julien; Drieux, Fanny; Veresezan, Elena-Liana; Bobée, Victor; Rainville, Vinciane; Bohers, Elodie; Sesques, Pierre; Haioun, Corinne; Durot, Eric; Bayaram, Michael; Rossi, Cédric; Martin, Laurent; Penther, Dominique; Kaltenbach, Sophie; Bruneau, Julie; Paillassa, Jérôme; Tournilhac, Olivier; Gower, Nicolas; Willaume, Alexandre; Antier, Chloe; Renaud, Loïc; Leveque, Emilie; Decazes, Pierre; Becker, Stéphanie; Tonnelet, David; Gaulard, Philippe; Tilly, Hervé; Molina, Thierry; Traverse-Glehen, Alexandra; Donzel, Marie; Ruminy, Philippe; Jardin, Fabrice.
Afiliación
  • Camus V; Centre Henri Becquerel, Rouen, France.
  • Viennot M; Centre Henri Becquerel, Rouen, France.
  • Viailly PJ; INSERM U1245, Rouen, France.
  • Drieux F; Centre Henri Becquerel, Rouen, France.
  • Veresezan EL; Centre Henri Becquerel, Rouen, France.
  • Bobée V; Rouen University Hospital, Rouen, France.
  • Rainville V; INSERM U1245, Centre Henri Becquerel, Rouen, France.
  • Bohers E; Inserm U1245, Centre Henri Becquerel, Rouen, France.
  • Sesques P; CHU Lyon Sud, HCL, Pierre Bénite, France.
  • Haioun C; CHU Henri Mondor, Créteil, France.
  • Durot E; Hôpital Robert Debré CHU de Reims, Reims cedex, France.
  • Bayaram M; Hôpital Robert Debré CHU de Reims, Reims cedex, France.
  • Rossi C; CHU Dijon, Dijon, France.
  • Martin L; CHU DIJON, Dijon, France.
  • Penther D; Centre Henri Becquerel, rouen, France.
  • Kaltenbach S; Hôpital Necker-Enfants Malades, Paris, France.
  • Bruneau J; Hopital Necker-Enfants malades; Universite Paris Descartes, Paris, France.
  • Paillassa J; CHU d'Angers, Angers, France.
  • Tournilhac O; CHU Estaing, Clermont-Fd, Chelter EA7453, CIC-1405, Université Clermont Auvergne, Clermont-Ferrand, France.
  • Gower N; CHU Lille, Lille, France.
  • Willaume A; Hôpital Saint Vincent de Paul, Lille, France.
  • Antier C; Nantes University Hospital, Nantes, France.
  • Renaud L; Gustave Roussy, France.
  • Leveque E; Centre Henri Becquerel, Rouen, France.
  • Decazes P; Centre Henri Becquerel, Rouen, France.
  • Becker S; Centre Henri Becquerel, Rouen, France.
  • Tonnelet D; Centre Henri Becquerel, Rouen, France.
  • Gaulard P; Hôpital Henri-Mondor, Créteil, France, Créteil, France.
  • Tilly H; Centre Henri Becquerel, Rouen, France.
  • Molina T; Necker-Enfants Malades University Hospital, AP-HP, Paris, France.
  • Traverse-Glehen A; Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite, France.
  • Donzel M; Hospices Civils de Lyon, Pierre Bénite, France.
  • Ruminy P; Centre Henri Becquerel, Rouen, France.
  • Jardin F; Centre Henri Becquerel, rouen, France.
Blood Adv ; 2024 Sep 18.
Article en En | MEDLINE | ID: mdl-39293080
ABSTRACT
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]).
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Blood Adv Año: 2024 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Blood Adv Año: 2024 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos