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

Simple item page
dc.citation.volumeNumber6en_US
dc.contributor.authorKüçük, C.en_US
dc.contributor.authorJiang, B.en_US
dc.contributor.authorHu X.en_US
dc.contributor.authorZhang W.en_US
dc.contributor.authorChan J.K.C.en_US
dc.contributor.authorXiao W.en_US
dc.contributor.authorLack, N.en_US
dc.contributor.authorAlkan, C.en_US
dc.contributor.authorWilliams J.C.en_US
dc.contributor.authorAvery, K.N.en_US
dc.contributor.authorKavak P.en_US
dc.contributor.authorScuto, A.en_US
dc.contributor.authorSen, E.en_US
dc.contributor.authorGaulard P.en_US
dc.contributor.authorStaudt L.en_US
dc.contributor.authorIqbal J.en_US
dc.contributor.authorZhang W.en_US
dc.contributor.authorCornish, A.en_US
dc.contributor.authorGong Q.en_US
dc.contributor.authorYang Q.en_US
dc.contributor.authorSun H.en_US
dc.contributor.authorD'Amore F.en_US
dc.contributor.authorLeppä, S.en_US
dc.contributor.authorLiu W.en_US
dc.contributor.authorFu, K.en_US
dc.contributor.authorDe Leval L.en_US
dc.contributor.authorMcKeithan, T.en_US
dc.contributor.authorChan W.C.en_US
dc.date.accessioned2016-02-08T10:19:49Z
dc.date.available2016-02-08T10:19:49Z
dc.date.issued2015en_US
dc.departmentDepartment of Computer Engineeringen_US
dc.description.abstractLymphomas 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. © 2015 Macmillan Publishers Limited. All rights reserved.en_US
dc.description.provenanceMade available in DSpace on 2016-02-08T10:19:49Z (GMT). No. of bitstreams: 1 bilkent-research-paper.pdf: 70227 bytes, checksum: 26e812c6f5156f83f0e77b261a471b5a (MD5) Previous issue date: 2015en
dc.identifier.doi10.1038/ncomms7025en_US
dc.identifier.issn20411723
dc.identifier.urihttp://hdl.handle.net/11693/23825
dc.language.isoEnglishen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionofhttp://dx.doi.org/10.1038/ncomms7025en_US
dc.source.titleNature Communicationsen_US
dc.subjecthistidineen_US
dc.subjectJanus kinase 2 inhibitoren_US
dc.subjectJanus kinase inhibitoren_US
dc.subjectmutant proteinen_US
dc.subjectphosphotyrosineen_US
dc.subjectSTAT5b proteinen_US
dc.subjectdisease treatmenten_US
dc.subjectinhibitionen_US
dc.subjectmolecular analysisen_US
dc.subjectmutationen_US
dc.subjectparthenogenesisen_US
dc.subjectproteinen_US
dc.subjecttumoren_US
dc.subjectArticleen_US
dc.subjectbinding affinityen_US
dc.subjectbinding siteen_US
dc.subjectcancer growthen_US
dc.subjectcontrolled studyen_US
dc.subjectgamma delta T lymphocyteen_US
dc.subjectgene mutationen_US
dc.subjecthumanen_US
dc.subjecthuman cellen_US
dc.subjectlymphoma cell lineen_US
dc.subjectmeasurementen_US
dc.subjectmolecular modelen_US
dc.subjectmutator geneen_US
dc.subjectnatural killer cellen_US
dc.subjectNK T cell lymphomaen_US
dc.subjectprotein phosphorylationen_US
dc.subjectSTAT3 geneen_US
dc.subjectSTAT5B geneen_US
dc.subjectsurface plasmon resonanceen_US
dc.subjectT cell lymphomaen_US
dc.titleActivating mutations of STAT5B and STAT3 in lymphomas derived from γδ-T or NK cellsen_US
dc.typeArticleen_US

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Activating mutations of STAT5B and STAT3 in lymphomas derived from γδ-T or NK cells.pdf
Size:
1.14 MB
Format:
Adobe Portable Document Format
Description:
Full printable version
Download

Collections

Department of Computer Engineering