{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T08:23:03Z","timestamp":1740126183976,"version":"3.37.3"},"reference-count":23,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,5,3]],"date-time":"2017-05-03T00:00:00Z","timestamp":1493769600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"government of Nepal"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Philadelphia chromosome\/<jats:styled-content style=\"fixed-case\">BCR<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">ABL<\/jats:styled-content>1 positive chronic myeloid leukaemia (<jats:styled-content style=\"fixed-case\">CML<\/jats:styled-content>) can be successfully treated with Glivec (Imatinib), which is available free of cost through the Glivec International Patient Assistance programme (<jats:styled-content style=\"fixed-case\">GIPAP<\/jats:styled-content>) to patients with proven <jats:styled-content style=\"fixed-case\">CML<\/jats:styled-content> without means to pay for the drug. We review the acquired mutations in the tyrosine kinase encoded by the <jats:italic>BCR\u2010ABL1<\/jats:italic> gene underlying Glivec failure or resistance in a cohort of 388 imatinib\u2010treated <jats:styled-content style=\"fixed-case\">CML<\/jats:styled-content> patients (149 Female and 239 male) registered between February 2003 and June 2016 in Nepal. Forty\u2010five patients (11 female 34 male) were studied; 18 different <jats:italic><jats:styled-content style=\"fixed-case\">BCR<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">ABL<\/jats:styled-content>1<\/jats:italic> mutations were seen in 33 patients. P\u2010loop mutation, Kinase domain and A\u2010loop mutations were seen in 9, 16 and 4 patients respectively. Other mutations were seen in five patients. A T315I mutation was the most common mutation, followed by F359V and M244V. Sixteen mutations showed intermediate activity to complete resistance to Glivec. Among the 45 patients evaluated for <jats:italic><jats:styled-content style=\"fixed-case\">BCR<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">ABL<\/jats:styled-content>1<\/jats:italic> mutations, 4 were lost to follow\u2010up, 14 died and 27 are still alive. Among the surviving patients, 16 are receiving Nilotinib, 5 Dasatinib and 3 Ponatinib, while 3 patients were referred to India, one of who received allogenic bone marrow transplantation. Understanding the spectrum of further acquired mutations in <jats:italic>BCR\u2010ABL1<\/jats:italic> may help to choose more specific targeted tyrosine kinase inhibitors that can be provided by GIPAP.<\/jats:p>","DOI":"10.1111\/bjh.14683","type":"journal-article","created":{"date-parts":[[2017,5,3]],"date-time":"2017-05-03T10:02:42Z","timestamp":1493805762000},"page":"1000-1007","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The use of Imatinib resistance mutation analysis to direct therapy in Philadelphia chromosome\/BCR\u2010ABL1 positive chronic myeloid leukaemia patients failing Imatinib treatment, in Patan Hospital, Nepal"],"prefix":"10.1111","volume":"177","author":[{"given":"Gyan K.","family":"Kayastha","sequence":"first","affiliation":[{"name":"Patan Academy of Health Science Patan Hospital Kathmandu Nepal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nora","family":"Ranjitkar","sequence":"additional","affiliation":[{"name":"Patan Academy of Health Science Patan Hospital Kathmandu Nepal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Radha","family":"Gurung","sequence":"additional","affiliation":[{"name":"Patan Academy of Health Science Patan Hospital Kathmandu Nepal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raj Kumar","family":"KC","sequence":"additional","affiliation":[{"name":"Patan Academy of Health Science Patan Hospital Kathmandu Nepal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjit","family":"Karki","sequence":"additional","affiliation":[{"name":"Patan Academy of Health Science Patan Hospital Kathmandu Nepal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roshan","family":"Shrestha","sequence":"additional","affiliation":[{"name":"Patan Academy of Health Science Patan Hospital 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and Transplant John Radcliffe Hospital Oxford UK"},{"name":"Radcliffe Department of Medicine John Radcliffe Hospital Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce","family":"Hayes","sequence":"additional","affiliation":[{"name":"Patan Academy of Health Science Patan Hospital Kathmandu Nepal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Zimmerman","sequence":"additional","affiliation":[{"name":"Patan Academy of Health Science Patan Hospital Kathmandu Nepal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1125-2743","authenticated-orcid":false,"given":"Buddha","family":"Basnyat","sequence":"additional","affiliation":[{"name":"Patan Academy of Health Science Patan Hospital Kathmandu Nepal"},{"name":"Oxford University Clinical Research Unit\u2010Nepal Centre for Tropical Medicine and Global Health University of Oxford Oxford 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