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

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State: Public
Version: Final published version
Serval ID
serval:BIB_68B017C9B01E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Activating mutations of STAT5B and STAT3 in lymphomas derived from γδ-T or NK cells.
Journal
Nature Communications
Author(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
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
6
Pages
6025
Language
english
Notes
Publication types: Journal Article Publication Status: epublish
Abstract
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
Yes
Create date
08/07/2015 9:37
Last modification date
20/08/2019 14:23
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