{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:08:45Z","timestamp":1772118525121,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,2,24]],"date-time":"2020-02-24T00:00:00Z","timestamp":1582502400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100009096","name":"Taiwan Clinical Oncology Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009096","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hematological Oncology"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>BCR\u2010ABL<\/jats:italic>\n                    mutations are associated with resistance to tyrosine kinase inhibitors (TKIs) in Philadelphia chromosome\u2010positive leukaemia. The emergence of these mutations in the era of second\u2010generation TKIs, such as dasatinib and nilotinib, remains an evolving field. We conducted a retrospective study to quantitatively characterize the BCR\u2010ABL transcript and mutation status during treatment with first\u2010generation and second\u2010generation TKI therapies.\n                    <jats:italic>BCR\u2010ABL<\/jats:italic>\n                    mutations were detected by direct sequencing for patients with Philadelphia chromosome\u2010positive leukaemia receiving TKI therapies. The efficacy of TKI therapy was quantitatively assessed by calculating the log reduction of BCR\u2010ABL transcripts, which was measured using real\u2010time quantitative polymerase chain reaction. Fisher's exact test was performed to analyse the associations of log reduction &lt;3 and mutation status. We found 35 patients harbouring 55 mutations of 43 different types, of which 30% occurred in patients receiving imatinib, 27% in nilotinib, and 43% in dasatinib. We found a novel germline mutation, N336\u2009N (AAC\u2794AAT), and two novel frameshift mutations, Asn358Thr fs*14 and Gly251Ala fs*16. T315I was the most common missense mutation, followed by V299L and F317L. Intron 8 35\u2010bp insertion was the most frequent frameshift mutation. Both missense and multiple\n                    <jats:italic>BCR\u2010ABL<\/jats:italic>\n                    mutations were significantly associated with worse molecular response compared with the molecular response of patients without mutation. Missense mutations, rather than frameshift, were associated with less log reduction, while the T315I, F317L, and T315A mutations were significantly correlated with poor log reduction. Collectively, amino acid substitutions at T315I, F317L, and T315A accounted for the majority of missense mutations and the loss of major molecular response. Mutation analysis is essential for patients receiving TKI therapy who exhibit an unfavourable response. The present study provided a landscape of\n                    <jats:italic>BCR\u2010ABL<\/jats:italic>\n                    mutations in the era of second\u2010generation TKIs.\n                  <\/jats:p>","DOI":"10.1002\/hon.2721","type":"journal-article","created":{"date-parts":[[2020,2,3]],"date-time":"2020-02-03T08:16:49Z","timestamp":1580717809000},"page":"390-398","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The landscape of\n                    <i>BCR\u2010ABL<\/i>\n                    mutations in patients with Philadelphia chromosome\u2010positive leukaemias in the era of second\u2010generation tyrosine kinase inhibitors"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4820-8500","authenticated-orcid":false,"given":"Sheng\u2010Hsuan","family":"Chien","sequence":"first","affiliation":[{"name":"Division of Transfusion Medicine, Department of Medicine, Taipei Veterans General Hospital  Taipei Taiwan"},{"name":"Faculty of Medicine National Yang\u2010Ming University  Taipei Taiwan"},{"name":"Institute of Clinical Medicine National Yang\u2010Ming University  Taipei Taiwan"},{"name":"Division of Hematology, Department of Medicine, Taipei Veterans General Hospital  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsueng\u2010Mei","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Transfusion Medicine, Department of Medicine, Taipei Veterans General Hospital  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Po\u2010Ming","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Food and Science and biotechnology National Chung Hsing University  Taichung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Po\u2010Shen","family":"Ko","sequence":"additional","affiliation":[{"name":"Faculty of Medicine National Yang\u2010Ming University  Taipei Taiwan"},{"name":"Division of Hematology, Department of Medicine, Taipei Veterans General Hospital  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9284-6665","authenticated-orcid":false,"given":"Jeong\u2010Shi","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Transfusion Medicine, Department of Medicine, Taipei Veterans General Hospital  Taipei Taiwan"},{"name":"Faculty of Medicine National Yang\u2010Ming University  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying\u2010Ju","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Transfusion Medicine, Department of Medicine, Taipei Veterans General Hospital  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li\u2010Hsuan","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Transfusion Medicine, Department of Medicine, Taipei Veterans General Hospital  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang\u2010Tsai","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Faculty of Medicine National Yang\u2010Ming University  Taipei Taiwan"},{"name":"Division of Hematology, Department of Medicine, Taipei Veterans General Hospital  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tzeon\u2010Jye","family":"Chiou","sequence":"additional","affiliation":[{"name":"Division of Transfusion Medicine, Department of Medicine, Taipei Veterans General Hospital  Taipei Taiwan"},{"name":"Faculty of Medicine National Yang\u2010Ming University  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jyh\u2010Pyng","family":"Gau","sequence":"additional","affiliation":[{"name":"Faculty of Medicine National Yang\u2010Ming University  Taipei Taiwan"},{"name":"Division of Hematology, Department of Medicine, Taipei Veterans General 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