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Previous studies have shown that the phosphatidylinositol 3\u2010kinase (<jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3K)\/Akt pathway is activated in <jats:styled-content style=\"fixed-case\">EBV<\/jats:styled-content>\u2010associated lymphomas and can be a novel therapeutic target. An oral dual inhibitor of <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3K<jats:italic>\u03b3<\/jats:italic> and <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3K<jats:italic>\u03b4<\/jats:italic>, duvelisib, is in clinical trials for the treatment of lymphoid malignancies. In this study, we evaluated how duvelisib affects the activity of the <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3K\/Akt signaling pathway and if it has antitumor effects in <jats:styled-content style=\"fixed-case\">EBV<\/jats:styled-content>\u2010associated lymphoma cell lines. We found that the <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3K\/Akt signaling pathway was activated in most of the B and T cell lymphoma cell lines tested. Additionally, duvelisib treatment inhibited cellular growth in the tested cell lines. Overall, B cell lines were more susceptible to duvelisib than T and <jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content> cell lines in vitro regardless of <jats:styled-content style=\"fixed-case\">EBV<\/jats:styled-content> infection. However, the additional influence of duvelisib on the tumor microenvironment was not assessed. Duvelisib treatment induced both apoptosis and cell cycle arrest in <jats:styled-content style=\"fixed-case\">EBV<\/jats:styled-content>\u2010positive and \u2010negative B cell lines, but not in T cell lines. Furthermore, duvelisib treatment reduced the expression of <jats:styled-content style=\"fixed-case\">EBV<\/jats:styled-content> lytic genes (<jats:styled-content style=\"fixed-case\">BZLF<\/jats:styled-content>1 and gp350\/220) in <jats:styled-content style=\"fixed-case\">EBV<\/jats:styled-content>\u2010positive B cell lines, suggesting that duvelisib suppresses the lytic cycle of <jats:styled-content style=\"fixed-case\">EBV<\/jats:styled-content> induced by B cell receptor signaling. However, duvelisib did not induce a remarkable change in the expression of <jats:styled-content style=\"fixed-case\">EBV<\/jats:styled-content> latent genes. These results may indicate that there is therapeutic potential for duvelisib administration in the treatment of <jats:styled-content style=\"fixed-case\">EBV<\/jats:styled-content>\u2010associated B cell lymphomas and other B cell malignancies.<\/jats:p>","DOI":"10.1002\/cam4.1311","type":"journal-article","created":{"date-parts":[[2018,3,9]],"date-time":"2018-03-09T15:32:54Z","timestamp":1520609574000},"page":"1275-1284","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Antitumor effects of duvelisib on Epstein\u2013Barr virus\u2010associated lymphoma cells"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1553-2539","authenticated-orcid":false,"given":"Jun\u2010ichi","family":"Kawada","sequence":"first","affiliation":[{"name":"Departments of Pediatrics Nagoya University Graduate School of Medicine  65 Tsurumai\u2010cho, Showa\u2010ku Nagoya 466\u20108550 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shotaro","family":"Ando","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics Nagoya University Graduate School of Medicine  65 Tsurumai\u2010cho, Showa\u2010ku Nagoya 466\u20108550 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Torii","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics Nagoya University Graduate School of Medicine  65 Tsurumai\u2010cho, Showa\u2010ku Nagoya 466\u20108550 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Departments of Virology Nagoya University Graduate School of Medicine  65 Tsurumai\u2010cho, Showa\u2010ku Nagoya 466\u20108550 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitaka","family":"Sato","sequence":"additional","affiliation":[{"name":"Departments of Virology Nagoya University Graduate School of Medicine  65 Tsurumai\u2010cho, Showa\u2010ku Nagoya 466\u20108550 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinori","family":"Ito","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics Nagoya University Graduate School of Medicine  65 Tsurumai\u2010cho, Showa\u2010ku Nagoya 466\u20108550 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kimura","sequence":"additional","affiliation":[{"name":"Departments of Virology Nagoya University Graduate School of Medicine  65 Tsurumai\u2010cho, Showa\u2010ku Nagoya 466\u20108550 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,3,9]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200008173430707"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1452"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdp064"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-10-381921"},{"key":"e_1_2_7_6_1","first-page":"549","article-title":"The Epstein\u2010Barr virus latent membrane protein\u20101 (LMP1) mediates activation of NF\u2010kappa B and cell surface phenotype via two effector regions in its carboxy\u2010terminal cytoplasmic domain","volume":"10","author":"Huen D. 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