Background and Aim:
Imatinib mesylate (IM) is a Bcr-Abl۱- 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 the type and frequency of kinase domain (KD) mutations in Iranian CML patients, and also the effects of these mutations on clinical outcomes.Methods: We analyzed ۱۰ different type of the
BCR-ABL۱ kinase domain mutations using ASO-PCR method in ۶۳ resistant patients to imatinib . The median duration of imatinib treatment was ۳۶ months ranging from ۱۰ to ۶۰ 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.۱۳۹۷.۵۶).Results: In this study, ۲۷ of ۶۳ (۴۲.۸۵%) resistant patients had mutations from ۱۰ different type . The most common mutation was H۳۹۶R( ۱۸ patients, ۲۸.۵۷%) in A-loop,the frequency of other mutations were: E۳۵۵G(۹.۵۲%); G۲۵۰E, E۲۵۵K and Y۲۵۳H (۶.۴%); T۳۱۵I (۴.۷۶%);M۲۴۴Vand M۳۵۱T (۳.۲%); E۲۵۵V and Y۲۵۳F(۱.۶%). ۱۱ of ۶۳ (۱۷.۴۶%) patients had two or more mutation. The OS from the start of IM treatment was not significantly different (P=۰.۰۸) between the patients with and without mutations. PFS from the start of IM treatment was correlated significantly with the presence of mutations (P= ۰.۰۳).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