Activating mutations of STAT5B and STAT3 in lymphomas derived from γδ-T or NK cells.

Détails

Ressource 1Télécharger: LDL_25586472.pdf (1121.29 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_68B017C9B01E
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Activating mutations of STAT5B and STAT3 in lymphomas derived from γδ-T or NK cells.
Périodique
Nature Communications
Auteur⸱e⸱s
Küçük C., Jiang B., Hu X., Zhang W., Chan J.K., Xiao W., Lack N., Alkan C., Williams J.C., Avery K.N., Kavak P., Scuto A., Sen E., Gaulard P., Staudt L., Iqbal J., Zhang W., Cornish A., Gong Q., Yang Q., Sun H., d'Amore F., Leppä S., Liu W., Fu K., de Leval L., McKeithan T., Chan W.C.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
6
Pages
6025
Langue
anglais
Notes
Publication types: Journal Article Publication Status: epublish
Résumé
Lymphomas arising from NK or γδ-T cells are very aggressive diseases and little is known regarding their pathogenesis. Here we report frequent activating mutations of STAT3 and STAT5B in NK/T-cell lymphomas (n=51), γδ-T-cell lymphomas (n=43) and their cell lines (n=9) through next generation and/or Sanger sequencing. STAT5B N642H is particularly frequent in all forms of γδ-T-cell lymphomas. STAT3 and STAT5B mutations are associated with increased phosphorylated protein and a growth advantage to transduced cell lines or normal NK cells. Growth-promoting activity of the mutants can be partially inhibited by a JAK1/2 inhibitor. Molecular modelling and surface plasmon resonance measurements of the N642H mutant indicate a marked increase in binding affinity of the phosphotyrosine-Y699 with the mutant histidine. This is associated with the prolonged persistence of the mutant phosphoSTAT5B and marked increase of binding to target sites. Our findings suggest that JAK-STAT pathway inhibition may represent a therapeutic strategy.
Pubmed
Web of science
Open Access
Oui
Création de la notice
08/07/2015 9:37
Dernière modification de la notice
20/08/2019 14:23
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