Peripheral T-cell lymphoma: molecular profiling recognizes subclasses and identifies prognostic markers

• Published in: Blood advances 2021-12, Vol.5 (24), p.5588-5598
• Main Authors: Rodríguez, Marta, Alonso-Alonso, Ruth, Tomás-Roca, Laura, Rodríguez-Pinilla, Socorro M., Manso-Alonso, Rebeca, Cereceda, Laura, Borregón, Jennifer, Villaescusa, Teresa, Córdoba, Raúl, Sánchez-Beato, Margarita, Fernández-Miranda, Ismael, Betancor, Isabel, Bárcena, Carmen, García, Juan F., Mollejo, Manuela, García-Cosio, Mónica, Martin-Acosta, Paloma, Climent, Fina, Caballero, Dolores, de la Fuente, Lorena, Mínguez, Pablo, Kessler, Linda, Scholz, Catherine, Gualberto, Antonio, Mondéjar, Rufino, Piris, Miguel A.
• Format: Article
• Language: English
• Subjects: Humans; Immunoblastic Lymphadenopathy; Lymphoid Neoplasia; Lymphoma, T-Cell, Peripheral - diagnosis; Lymphoma, T-Cell, Peripheral - genetics; Mutation; Phenotype; Prognosis
• ISSN: 2473-9529; 2473-9537
• DOI: 10.1182/bloodadvances.2021005171

Peripheral T-cell lymphoma (PTCL) is a clinically aggressive disease, with a poor response to therapy and a low overall survival rate of approximately 30% after 5 years. We have analyzed a series of 105 cases with a diagnosis of PTCL using a customized NanoString platform (NanoString Technologies, Seattle, WA) that includes 208 genes associated with T-cell differentiation, oncogenes and tumor suppressor genes, deregulated pathways, and stromal cell subpopulations. A comparative analysis of the various histological types of PTCL (angioimmunoblastic T-cell lymphoma [AITL]; PTCL with T follicular helper [TFH] phenotype; PTCL not otherwise specified [NOS]) showed that specific sets of genes were associated with each of the diagnoses. These included TFH markers, cytotoxic markers, and genes whose expression was a surrogate for specific cellular subpopulations, including follicular dendritic cells, mast cells, and genes belonging to precise survival (NF-κB) and other pathways. Furthermore, the mutational profile was analyzed using a custom panel that targeted 62 genes in 76 cases distributed in AITL, PTCL-TFH, and PTCL-NOS. The main differences among the 3 nodal PTCL classes involved the RHOAG17V mutations (P < .0001), which were approximately twice as frequent in AITL (34.09%) as in PTCL-TFH (16.66%) cases but were not detected in PTCL-NOS. A multivariate analysis identified gene sets that allowed the series of cases to be stratified into different risk groups. This study supports and validates the current division of PTCL into these 3 categories, identifies sets of markers that can be used for a more precise diagnosis, and recognizes the expression of B-cell genes as an IPI-independent prognostic factor for AITL. •Gene expression and mutational analysis confirm the differences among the 3 peripheral TCL subclasses: AITL, PTCL-NOS, and PTCL-TFH.•The expression of a gene set, including B-cell genes, is an IPI-independent prognostic factor for AITL cases. [Display omitted]