{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T04:25:50Z","timestamp":1786422350612,"version":"build-2736575974"},"reference-count":43,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"7","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Global Oncology"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:sec><jats:title>PURPOSE<\/jats:title><jats:p> Despite the successes achieved in chronic myeloid leukemia (CML) with tyrosine kinase inhibitor (TKI) therapy, resistance remains an obstacle. The most common mechanism of resistance is the acquisition of a point mutation in the BCR-ABL kinase domain. Few studies have reported African patients with CML in regard to such mutations. We here report the types of BCR-ABL mutations in Ethiopian imatinib-resistant patients with CML and their outcome. <\/jats:p><\/jats:sec><jats:sec><jats:title>PATIENTS AND METHODS<\/jats:title><jats:p> Patients with CML with a diagnosis of imatinib resistance who were tested for BCR-ABL mutation between 2014 and September 2019 were included. <\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p> A total of 962 cases of CML on imatinib therapy were reviewed and 164 cases of failure were found. Of these, only 31 cases (19%) had mutation analysis performed. Most cases (94%) were secondary failures. At the time of CML diagnosis, the median age was 33 years and the majority presented with features of advanced-phase disease. Of the 31 patients, 22 mutations were found (65%). The types of mutations detected were as follows: non\u2013P-loop mutations 36% (11), P-loop mutations 13% (four), and alternatively spliced BCR-ABL variants 23% (seven). The splice variant frequently detected was BCR-ABL<jats:sup>35INS<\/jats:sup> (20%). Twenty-six of the 31 patients (84%) were switched to second-line TKIs, whereas in four patients (13%), imatinib dose escalation was done. Overall, the outcome revealed that 16 patients (52%) were alive with complete hematologic response, whereas 12 patients (39%) had died. All patients who expressed BCR-ABL1<jats:sup>35INS<\/jats:sup> were treated with second-line TKIs, and two of them (33%) had died because of disease progression. <\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p> In Ethiopia, CML affects the young and point mutations were frequently detected in imatinib-resistant patients. BCR-ABL1 <jats:sup>35INS<\/jats:sup> was also prevalent and associated with disease progression. <\/jats:p><\/jats:sec>","DOI":"10.1200\/go.21.00058","type":"journal-article","created":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T19:59:59Z","timestamp":1626983999000},"page":"1187-1193","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":20,"title":["Spectrum of BCR-ABL Mutations and Treatment Outcomes in Ethiopian Imatinib-Resistant Patients With Chronic Myeloid Leukemia"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4270-9424","authenticated-orcid":false,"given":"Fisihatsion","family":"Tadesse","sequence":"first","affiliation":[{"name":"Addis Ababa University College of Health Sciences, Addis Ababa, Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Getahun","family":"Asres","sequence":"additional","affiliation":[{"name":"University of Gondar, College of Medicine and Health Sciences, Gondar, Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulaziz","family":"Abubeker","sequence":"additional","affiliation":[{"name":"Addis Ababa University College of Health Sciences, Addis Ababa, Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amha","family":"Gebremedhin","sequence":"additional","affiliation":[{"name":"Addis Ababa University College of Health Sciences, Addis Ababa, Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerald","family":"Radich","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Research Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"b1","doi-asserted-by":"publisher","DOI":"10.1038\/243290a0"},{"key":"b2","doi-asserted-by":"publisher","DOI":"10.1016\/j.disamonth.2012.01.007"},{"key":"b3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199907153410306"},{"key":"b4","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.26679"},{"key":"b6","doi-asserted-by":"publisher","DOI":"10.1016\/j.beha.2009.07.007"},{"key":"b7","first-page":"2155","volume":"8","author":"Tadwalkar S","year":"2017","journal-title":"J Blood Disord Transfus"},{"key":"b8","doi-asserted-by":"publisher","DOI":"10.1200\/jgo.18.30600"},{"key":"b9","doi-asserted-by":"publisher","DOI":"10.1016\/j.canep.2013.01.002"},{"key":"b10","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0213557"},{"key":"b11","doi-asserted-by":"publisher","DOI":"10.1182\/hematology.2019000050"},{"key":"b12","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2020.100257"},{"key":"b13","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(07)70342-X"},{"key":"b14","doi-asserted-by":"publisher","DOI":"10.1159\/000210060"},{"key":"b15","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-1516"},{"key":"b16","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2013.09.011"},{"key":"b17","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-12-326405"},{"key":"b18","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2126"},{"key":"b19","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-08-215939"},{"key":"b20","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-020-0776-2"},{"key":"b21","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2018.0071"},{"key":"b22","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-62703-357-2_2"},{"key":"b23","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-013-1937-4"},{"key":"b24","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2011.056721"},{"key":"b25","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdu490"},{"key":"b26","doi-asserted-by":"publisher","DOI":"10.4172\/2329-6917.1000106"},{"key":"b27","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-010-1039-5"},{"key":"b28","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-1516"},{"key":"b29","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404318"},{"key":"b30","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2016.1157868"},{"key":"b31","first-page":"79","volume":"1","author":"Oyekunle A","year":"2010","journal-title":"Afr J Haematol Oncol"},{"key":"b32","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-09-2896"},{"key":"b33","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.16.9953"},{"key":"b34","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2016.08.006"},{"key":"b35","doi-asserted-by":"publisher","DOI":"10.2353\/jmoldx.2008.070128"},{"key":"b36","doi-asserted-by":"publisher","DOI":"10.1080\/10245332.2018.1507883"},{"key":"b37","doi-asserted-by":"publisher","DOI":"10.3343\/alm.2012.32.6.452"},{"key":"b38","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc061882"},{"key":"b39","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-08-0482"},{"key":"b40","doi-asserted-by":"publisher","DOI":"10.1111\/cas.13353"},{"key":"b41","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2008.65"},{"key":"b42","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-02-269233"},{"key":"b43","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-05-349191"},{"key":"b44","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-10-0595"}],"container-title":["JCO Global Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/GO.21.00058","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,29]],"date-time":"2022-05-29T08:14:20Z","timestamp":1653812060000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/GO.21.00058"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12]]},"references-count":43,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["10.1200\/GO.21.00058"],"URL":"https:\/\/doi.org\/10.1200\/go.21.00058","relation":{},"ISSN":["2687-8941"],"issn-type":[{"value":"2687-8941","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12]]},"assertion":[{"value":"2021-02-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-12","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}