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

2021; Elsevier BV; Volume: 5; Issue: 24 Linguagem: Inglês

10.1182/bloodadvances.2021005171

2473-9537

Marta Rodríguez, Ruth Alonso‐Alonso, Laura Tomás‐Roca, Socorro María Rodríguez‐Pinilla, Rebeca Manso-Alonso, Laura Cereceda, Jennifer Borregón, Teresa Villaescusa, Raúl Córdoba, Margarita Sánchez‐Beato, Ismael Fernández‐Miranda, Isabel Betancor, Carmen Bárcena, Juan F. Garcı́a, Manuela Mollejo, Mónica García‐Cosío, Paloma Martín, Fina Climent, Dolores Caballero, Lorena de la Fuente-Tomás, Pablo Mínguez, Linda Kessler, Catherine Scholz, Antonio Gualberto, R. Mondéjar, Miguel Á. Piris,

Cutaneous lymphoproliferative disorders research

Abstract 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.