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Molecular basis of targeted therapy in T/NKcell lymphoma/leukemia: A comprehensive genomic and immunohistochemical analysis of a panel of 33 cell lines

Abstract: T and NK-cell lymphoma is a collection of aggressive disorders with unfavorable outcome, in which targeted treatments are still at a preliminary phase. To gain deeper insights into the deregulated mechanisms promoting this disease, we searched a panel of 31 representative T-cell and 2 NK-cell lymphoma/leukemia cell lines for predictive markers of response to targeted therapy. To this end, targeted sequencing was performed alongside the expression of specific biomarkers corresponding to potentially activated survival pathways. The study identified TP53, NOTCH1 and DNMT3A as the most frequently mutated genes. We also found common alterations in JAK/STAT and epigenetic pathways. Immunohistochemical analysis showed nuclear accumulation of MYC (in 85% of the cases), NFKB (62%), p-STAT (44%) and p-MAPK (30%). This panel of cell lines captures the complexity of T/NK-cell lymphoproliferative processes samples, with the partial exception of AITL cases. Integrated mutational and immunohistochemical analysis shows that mutational changes cannot fully explain the activation of key survival pathways and the resulting phenotypes. The combined integration of mutational/expression changes forms a useful tool with which new compounds may be assayed.

Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria

 Fuente: PLoS One. 2017 May 15;12(5): e0177524

Editorial: Public Library of Science

 Fecha de publicación: 15/05/2017

Nº de páginas: 14

Tipo de publicación: Artículo de Revista

 DOI: 10.1371/journal.pone.0177524

ISSN: 1932-6203

Autores/as

MONDEJAR, RUFINO

PÉREZ, CRISTINA

ARANTZA ONAINDIA PEREZ

MARTÍNEZ, NEREA

GONZÁLEZ RINCÓN, JULIA

PISONERO, HELENA

CERECEDA, LAURA

SÁNCHEZ BEATO, MARGARITA

MIGUEL ANGEL PIRIS PINILLA