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To investigate the influence of dasatinib on signal transduction pathways, we investigated the changes in <jats:styled-content style=\"fixed-case\">JAK<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>, mitogen\u2010activated protein kinase (<jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content>), and <jats:styled-content style=\"fixed-case\">AKT<\/jats:styled-content> in cytotoxic lymphocytes, including natural killer (<jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content>) cells and cytotoxic T lymphocytes (<jats:styled-content style=\"fixed-case\">CTL<\/jats:styled-content>s), before and after dasatinib treatment in chronic myeloid leukemia patients. Among a total of 30 patients, 18 were treated with dasatinib, nine with imatinib, and three with nilotinib. At constitutive levels, the expression of phosphorylated proteins, <jats:styled-content style=\"fixed-case\">pSTAT<\/jats:styled-content>1, <jats:styled-content style=\"fixed-case\">pSTAT<\/jats:styled-content>3, and <jats:styled-content style=\"fixed-case\">pERK<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content> cells and <jats:styled-content style=\"fixed-case\">pSTAT<\/jats:styled-content>3 in <jats:styled-content style=\"fixed-case\">CTL<\/jats:styled-content>s, was significantly higher in dasatinib\u2010treated patients. Among the patients evaluated, only dasatinib\u2010treated patients showed inhibition of multiple signaling pathways after taking a tyrosine kinase inhibitor. The magnitude of <jats:styled-content style=\"fixed-case\">pERK<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">pAKT<\/jats:styled-content> inhibition was closely associated with an increase in <jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content> cells and <jats:styled-content style=\"fixed-case\">CTL<\/jats:styled-content>s, respectively, after taking a tyrosine kinase inhibitor. Those responses were more evident in patients with cytomegalovirus IgG positivity. In this study, we demonstrated for the first time, the influence of dasatinib on cell events in cytotoxic lymphocytes in vivo and explained the possible underlying mechanism that results in lymphocyte mobilization after dasatinib treatment.<\/jats:p>","DOI":"10.1002\/cam4.925","type":"journal-article","created":{"date-parts":[[2016,10,13]],"date-time":"2016-10-13T13:14:30Z","timestamp":1476364470000},"page":"3223-3234","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Direct effect of dasatinib on signal transduction pathways associated with a rapid mobilization of cytotoxic lymphocytes"],"prefix":"10.1002","volume":"5","author":[{"given":"Noriyoshi","family":"Iriyama","sequence":"first","affiliation":[{"name":"Division of Hematology and Rheumatology Department of Medicine Nihon University School of Medicine  Tokyo 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