{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T19:54:52Z","timestamp":1792958092831,"version":"4.5.0"},"reference-count":32,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,5,29]],"date-time":"2018-05-29T00:00:00Z","timestamp":1527552000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007132","name":"Otsuka Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007132","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004336","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2018,7]]},"abstract":"Tyrosine kinase inhibitors (TKI<\/jats:styled-content>) are used for primary therapy in patients with newly diagnosed CML<\/jats:styled-content>. However, a reliable method for optimal selection of a TKI<\/jats:styled-content> from the viewpoint of drug sensitivity of CML<\/jats:styled-content> cells has not been established. We have developed a FRET<\/jats:styled-content>\u2010based drug sensitivity test in which a CrkL\u2010derived fluorescent biosensor efficiently quantifies the kinase activity of BCR<\/jats:styled-content>\u2010ABL<\/jats:styled-content> of living cells and sensitively evaluates the inhibitory activity of a TKI<\/jats:styled-content> against BCR<\/jats:styled-content>\u2010ABL<\/jats:styled-content>. Here, we validated the utility of the FRET<\/jats:styled-content>\u2010based drug sensitivity test carried out at diagnosis for predicting the molecular efficacy. Sixty\u2010two patients with newly diagnosed chronic phase CML<\/jats:styled-content> were enrolled in this study and treated with dasatinib. Bone marrow cells at diagnosis were subjected to FRET<\/jats:styled-content> analysis. The \u0394FRET<\/jats:styled-content> value was calculated by subtraction of FRET<\/jats:styled-content> efficiency in the presence of dasatinib from that in the absence of dasatinib. Treatment response was evaluated every 3 months by the BCR<\/jats:styled-content>\u2010ABL<\/jats:styled-content>1<\/jats:italic> International Scale. Based on the \u0394FRET<\/jats:styled-content> value and molecular response, a threshold of the \u0394FRET<\/jats:styled-content> value in the top 10% of FRET<\/jats:styled-content> efficiency was set to 0.31. Patients with \u0394FRET<\/jats:styled-content> value \u22650.31 had significantly superior molecular responses (MMR<\/jats:styled-content> at 6 and 9 months and both MR<\/jats:styled-content>4 and MR<\/jats:styled-content>4.5 at 6, 9, and 12 months) compared with the responses in patients with \u0394FRET<\/jats:styled-content> value <0.31. These results suggest that the FRET<\/jats:styled-content>\u2010based drug sensitivity test at diagnosis can predict early and deep molecular responses. This study is registered with UMIN<\/jats:styled-content> Clinical Trials Registry (UMIN<\/jats:styled-content>000006358).<\/jats:p>","DOI":"10.1111\/cas.13625","type":"journal-article","created":{"date-parts":[[2018,5,2]],"date-time":"2018-05-02T23:56:37Z","timestamp":1525305397000},"page":"2256-2265","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Pretreatment evaluation of fluorescence resonance energy transfer\u2010based drug sensitivity test for patients with chronic myelogenous leukemia treated with dasatinib"],"prefix":"10.1111","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7455-5824","authenticated-orcid":false,"given":"Takeshi","family":"Kondo","sequence":"first","affiliation":[{"name":"Department of Hematology Faculty of Medicine and Graduate School of Medicine Hokkaido University Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"Fujioka","sequence":"additional","affiliation":[{"name":"Department of Cell Physiology Faculty of Medicine and Graduate School of Medicine Hokkaido University Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masumi","family":"Tsuda","sequence":"additional","affiliation":[{"name":"Department of Cancer Pathology Faculty of Medicine and Graduate School of Medicine Hokkaido University Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazunori","family":"Murai","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology Department of Internal Medicine Iwate Medical University School of Medicine Morioka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Division of Hematology Aomori Prefectural Central Hospital Aomori Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuto","family":"Miyagishima","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Japan Labour Health and Welfare Organization Kushiro Rosai Hospital Kushiro Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motohiro","family":"Shindo","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hematology\/Oncology Asahikawa Medical University Asahikawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Nagashima","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine\/General Medicine Kitami Red Cross Hospital Kitami Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Wakasa","sequence":"additional","affiliation":[{"name":"Division of Hematology Hokkaido P.W.F.A.C. Obihiro\u2010Kosei General Hospital Obihiro Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nozomu","family":"Fujimoto","sequence":"additional","affiliation":[{"name":"Division of Hematology Kaisei Hospital Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Hematology Sapporo City General Hospital Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masakatsu","family":"Yonezumi","sequence":"additional","affiliation":[{"name":"Department of Hematology Hokkaido Cancer Center Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Souichi","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Nihonkai General Hospital Sakata 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