机构：[1]Department of Pathology, City of Hope Medical Center, Duarte, California 91010, USA.[2]Department of Pathology, West China Hospital of Sichuan University, Chengdu 610041, China.四川大学华西医院[3]Department of Pathology, Queen Elizabeth Hospital, Hong Kong, China.[4]Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, Food and Drug Administration, Maryland 20993, USA.[5]Department of Pharmacology, Koc University, Istanbul 34450, Turkey.[6]Department of Computer Engineering, Bilkent University, Ankara 06800, Turkey.[7]Department of Molecular Medicine, Beckman Research Institute of City of Hope, Duarte, California 91010, USA.[8]Department of Computer Engineering, Boğaziçi University, İstanbul 34342, Turkey.[9]Département de Pathologie, Groupe Henri-Mondor Albert-Chenevier, Inserm U955, Université Paris Est, Créteil 94000, France.[10]Molecular Biology of Lymphoid Malignancies Section, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA.[11]Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68198-3135, USA.[12]Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska 68198-5805, USA.[13]Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100029, China.[14]Department of Hematology, Aarhus University Hospital, Aarhus 8000, Denmark.[15]Department of Oncology, Helsinki University Central Hospital, PO Box 180, Helsinki 00029, Finland.[16]Pathologie Clinique Institut, Universitaire de Pathologie rue du Bugnon 25, CH 1011 Lausanne, Switzerland.
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.
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第一作者：
第一作者机构：[1]Department of Pathology, City of Hope Medical Center, Duarte, California 91010, USA.
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推荐引用方式(GB/T 7714)：
Küçük Can,Jiang Bei,Hu Xiaozhou,et al.Activating mutations of STAT5B and STAT3 in lymphomas derived from γδ-T or NK cells.[J].Nature communications.2015,6:6025.doi:10.1038/ncomms7025.
APA：
Küçük Can,Jiang Bei,Hu Xiaozhou,Zhang Wenyan,Chan John K C...&Chan Wing C.(2015).Activating mutations of STAT5B and STAT3 in lymphomas derived from γδ-T or NK cells..Nature communications,6,
MLA：
Küçük Can,et al."Activating mutations of STAT5B and STAT3 in lymphomas derived from γδ-T or NK cells.".Nature communications 6.(2015):6025
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