{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T03:38:36Z","timestamp":1785209916638,"version":"3.55.0"},"reference-count":46,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2017,9,21]],"date-time":"2017-09-21T00:00:00Z","timestamp":1505952000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008792","name":"Novartis Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008792","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2017,11]]},"abstract":"Treatment with tyrosine kinase inhibitors (TKI<\/jats:styled-content>) may sequentially induce TKI<\/jats:styled-content>\u2010resistant BCR<\/jats:styled-content>\u2010ABL<\/jats:styled-content><\/jats:italic> mutants in chronic myeloid leukemia (CML<\/jats:styled-content>). Conventional PCR<\/jats:styled-content> monitoring of BCR<\/jats:styled-content>\u2010ABL<\/jats:styled-content><\/jats:italic> is an important indicator to determine therapeutic intervention for preventing disease progression. However, PCR<\/jats:styled-content> cannot separately quantify amounts of BCR<\/jats:styled-content>\u2010ABL<\/jats:styled-content><\/jats:italic> and its mutants, including alternatively spliced BCR<\/jats:styled-content>\u2010ABL<\/jats:styled-content><\/jats:italic> with an insertion of 35 intronic nucleotides (BCR<\/jats:styled-content>\u2010<\/jats:italic>ABL<\/jats:italic>I<\/jats:italic><\/jats:sup><\/jats:styled-content>ns35bp<\/jats:italic><\/jats:sup>) between ABL<\/jats:styled-content><\/jats:italic> exons 8 and 9, which introduces the premature termination and loss of kinase activity. To assess the clinical impact of BCR<\/jats:styled-content>\u2010ABL<\/jats:styled-content><\/jats:italic> mutants, we performed deep sequencing analysis of BCR<\/jats:styled-content>\u2010ABL<\/jats:styled-content><\/jats:italic> transcripts of 409 samples from 37 patients with suboptimal response to frontline imatinib who were switched to nilotinib. At baseline, TKI<\/jats:styled-content>\u2010resistant mutations were documented in 3 patients, whereas BCR<\/jats:styled-content>\u2010<\/jats:italic>ABL<\/jats:italic>I<\/jats:italic><\/jats:sup><\/jats:styled-content>ns35bp<\/jats:italic><\/jats:sup> was detected in all patients. After switching to nilotinib, both BCR<\/jats:styled-content>\u2010ABL<\/jats:styled-content><\/jats:italic> and BCR<\/jats:styled-content>\u2010<\/jats:italic>ABL<\/jats:italic>I<\/jats:italic><\/jats:sup><\/jats:styled-content>ns35bp<\/jats:italic><\/jats:sup> became undetectable in 3 patients who attained complete molecular response (CMR<\/jats:styled-content>), whereas in the remaining all 34 patients, BCR<\/jats:styled-content>\u2010<\/jats:italic>ABL<\/jats:italic>I<\/jats:italic><\/jats:sup><\/jats:styled-content>ns35bp<\/jats:italic><\/jats:sup> was persistently detected, and minimal residual disease (MRD<\/jats:styled-content>) fluctuated at low but detectable levels. PCR<\/jats:styled-content> monitoring underestimated molecular response in 5 patients whose BCR<\/jats:styled-content>\u2010<\/jats:italic>ABL<\/jats:italic>I<\/jats:italic><\/jats:sup><\/jats:styled-content>ns35bp<\/jats:italic><\/jats:sup> was persisted, although BCR<\/jats:styled-content>\u2010<\/jats:italic>ABL<\/jats:italic>I<\/jats:italic><\/jats:sup><\/jats:styled-content>ns35bp<\/jats:italic><\/jats:sup> does not definitively mark TKI<\/jats:styled-content> resistance. Therefore, quantification of BCR<\/jats:styled-content>\u2010<\/jats:italic>ABL<\/jats:italic>I<\/jats:italic><\/jats:sup><\/jats:styled-content>ns35bp<\/jats:italic><\/jats:sup> is useful for evaluating \u201cfunctional\u201d MRD<\/jats:styled-content> and determining the effectiveness of TKI<\/jats:styled-content> with accuracy.<\/jats:p>","DOI":"10.1111\/cas.13353","type":"journal-article","created":{"date-parts":[[2017,8,12]],"date-time":"2017-08-12T07:46:36Z","timestamp":1502523996000},"page":"2204-2212","source":"Crossref","is-referenced-by-count":16,"title":["Persistent detection of alternatively spliced BCR<\/scp>\u2010ABL<\/scp><\/i> variant results in a failure to achieve deep molecular response"],"prefix":"10.1111","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4908-1636","authenticated-orcid":false,"given":"Junichiro","family":"Yuda","sequence":"first","affiliation":[{"name":"Department of Medicine and Biosystemic Science Kyushu University Graduate School of Medical Science Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiro","family":"Miyamoto","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science Kyushu University Graduate School of Medical Science Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Odawara","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science Kyushu University Graduate School of Medical Science Fukuoka Japan"},{"name":"Department of Advanced Medical Initiatives Faculty of Medical Sciences Kyushu University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuyuki","family":"Ohkawa","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical Initiatives Faculty of Medical Sciences Kyushu University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichiro","family":"Semba","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science Kyushu University Graduate School of Medical Science Fukuoka Japan"},{"name":"Department of Advanced Medical Initiatives Faculty of Medical Sciences Kyushu University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayasu","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science Kyushu University Graduate School of Medical Science Fukuoka Japan"},{"name":"Department of Advanced Medical Initiatives Faculty of Medical Sciences Kyushu University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Miyamura","sequence":"additional","affiliation":[{"name":"Department of Hematology Japanese Red Cross Nagoya Daiichi Hospital Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsune","family":"Tanimoto","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Respiratory Medicine Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhito","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Clinical Research and Department of Hematology and Cell Therapy Aichi Cancer Center Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Taniwaki","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology Department of Medicine Kyoto Prefectural University of Medicine Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Akashi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science Kyushu University Graduate School of Medical Science Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,9,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0596-561"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa062867"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-03-273979"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2014.1.234"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1159\/000210060"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-08-0482"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-11-4687"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.26.5819"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.2353\/jmoldx.2008.070128"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa055229"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-06-162388"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2013.10.022"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2016.08.006"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-10-0595"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-05-349191"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403135"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2016.09.009"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-05-501569"},{"key":"e_1_2_7_20_1","first-page":"1","article-title":"Long\u2010range PCR in next\u2010generation sequencing: comparison of six enzymes and evaluation on the MiSeq sequencer","volume":"4","author":"Jia H","year":"2014","journal-title":"Sci Rep"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2009-10-3-r25"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2013-14-4-r36"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp352"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr509"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq033"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-05-577593"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11899-015-0260-7"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-12-615757"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-03-580027"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.20.1533"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beha.2014.04.002"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003656"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-01-550020"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-06-435669"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-11-468348"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70233-3"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.48.5797"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(15)00196-9"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-09-742205"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI35721"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI43605"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-013-1318-8"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/2050-7771-2-6"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10496"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.11.056"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-015-1747-7"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcas.13353","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.13353","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cas.13353","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.13353","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T22:09:49Z","timestamp":1694124589000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.13353"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,21]]},"references-count":46,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2017,11]]}},"alternative-id":["10.1111\/cas.13353"],"URL":"https:\/\/doi.org\/10.1111\/cas.13353","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,21]]}}}