STAT3 and STAT5B Mutations in T/NK-Cell Chronic Lymphoproliferative Disorders of Large Granular Lymphocytes (LGL): Association with Disease Features

[EN]STAT3 and STAT5B (STAT3/STAT5B) mutations are the most common mutations in T-cell large granular lymphocytic leukemia (T-LGLL) and chronic lymphoproliferative disorders of NK cells (CLPD-NK), but their clinical impact remains unknown. We investigated the frequency and type of STAT3/STAT5B mutati...

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Detalles Bibliográficos
Autores: Muñoz García, Noemi, Jara Acevedo, María, Bárcena, Paloma, Pontes Geraz Caldas, Carolina, Bárcena Carrasco, Paloma, López, Antonio, Puig, Noemí, Alcoceba Sánchez, Miguel, Fernández, Paula, Villamor, Neus, Flores Montero, Juan Alejandro, Gómez, Karoll, Lemes, María Angelina, Hernández, José Carlos, Álvarez‐Twose, Iván, Guerra, José Luis, González Díaz, Marcos, Orfao de Matos Correia e Vale, José Alberto, Almeida Parra, Julia María
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universidad de Salamanca (USAL)
Repositorio:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:gredos.usal.es:10366/168636
Acceso en línea:http://hdl.handle.net/10366/168636
Access Level:acceso abierto
Palabra clave:STAT3 and STAT5b mutations
LGL leukemia
STAT5 Transcription Factor
T-Lymphocytes
Mutation
Leukemia, Large Granular Lymphocytic
STAT3 Transcription Factor
leucemia de linfocitos grandes granulares
mutación
linfocitos T
factor de transcripción STAT3
factor de transcripción STAT5
Descripción
Sumario:[EN]STAT3 and STAT5B (STAT3/STAT5B) mutations are the most common mutations in T-cell large granular lymphocytic leukemia (T-LGLL) and chronic lymphoproliferative disorders of NK cells (CLPD-NK), but their clinical impact remains unknown. We investigated the frequency and type of STAT3/STAT5B mutations in FACS-sorted populations of expanded T/NK-LGL from 100 (82 clonal; 6 oligoclonal; 12 polyclonal) patients, and its relationship with disease features. Seventeen non-LGL T-CLPD patients and 628 age-matched healthy donors were analyzed as controls. STAT3 (n = 30) and STAT5B (n = 1) mutations were detected in 28/82 clonal T/NK-LGLL patients (34%), while absent (0/18, 0%) among oligoclonal/polyclonal LGL-lymphocytosis. Mutations were found across all diagnostic subgroups: TCD8+-LGLL, 36%; CLPD-NK, 38%; TCD4+-LGLL, 7%; Tαβ+DP-LGLL, 100%; Tαβ+DN-LGLL, 50%; Tγδ+-LGLL, 44%. STAT3-mutated T-LGLL/CLPD-NK showed overall reduced (p < 0.05) blood counts of most normal leukocyte subsets, with a higher rate (vs. nonmutated LGLL) of neutropenia (p = 0.04), severe neutropenia (p = 0.02), and cases requiring treatment (p = 0.0001), together with a shorter time-to-therapy (p = 0.0001), particularly in non-Y640F STAT3-mutated patients. These findings confirm and extend on previous observations about the high prevalence of STAT3 mutations across different subtypes of LGLL, and its association with a more marked decrease of all major blood-cell subsets and a shortened time-to-therapy.

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