Prevalence of Bcr-Abl1 Mutations and Clinical Outcomes in Iranian Patients With Chronic Myeloid Leukemia on Imatinib

Background and aim: imatinib mesylate (im) is a bcr-abl1- targeting drug at the forefront of the cml patients treatment. resistance to im has been attributed to multiple mechanisms including bcr-abl dependent and independent mechanisms. the mutations are the most important factor in development of imatinib-resistance in cml patients. the present study was designed to evaluate thetype and frequency of kinase domain (kd) mutations in iranian cml patients, and also the effects of these mutations on clinical outcomes.methods: we analyzed 10 different type of the bcr-abl1 kinase domain mutations using aso-pcr method in 63 resistant patients to imatinib . the median duration of imatinib treatment was 36 months ranging from 10 to 60 months. overall survival (os) was calculated from the initiation of imatinib therapy to death from any cause. time to progression was determined as the time from the start of imatinib treatment until the start of the evolution of advanced phase cml, loss of chr or complete cyr, or death. os and progression-free survival (pfs) were measured by using kaplan-meier method. the study was approved by the pasteur institute of iran ethical committee (ir.pii.rec.1397.56).results: in this study, 27 of 63 (42.85%) resistant patients had mutations from 10 different type . the most common mutation was h396r( 18 patients, 28.57%) in a-loop,the frequency of other mutations were: e355g(9.52%); g250e, e255k and y253h (6.4%); t315i (4.76%);m244vand m351t (3.2%); e255v and y253f(1.6%). 11 of 63 (17.46%) patients had two or more mutation. the os from the start of im treatment was not significantly different (p=0.08) between the patients with and without mutations. pfs from the start of im treatment was correlated significantly with the presence of mutations (p= 0.03).conclusion: we conclude that bcr-abl mutations are associated with the resistance in iranian population and the patients with mutation are in risk of disease progression. identification of kd mutations is necessary in order to manage alternative treatment in such cml patients.