Mutation Profiling of BCR-ABL Kinase Domain in Chronic Myeloid Leukaemia Patients with Imatinib Resistance

Abstract Objective: Emergence of mutation in the BCR-ABL kinase domain (KD) impairs imatinib mesylate (IM) binding capacity, thus contribute to IM resistance. Identification of these mutations is important for treatment decision and precision medicine in CML patients. Our study aims to determine the genomic landscape of BCR ABL KD mutations in CML patients with IM resistance. Result: BCR-ABL KD mutations were observed in 23 patients (26.7%). Fifteen different types of mutations have been identified; Y253H, E255K, T267A, K285I, A287T, M290R, F311I, T315I, F317L, F359V, F359I, F359C, K357T, A399T and E459K. We also discovered three novel mutations; M290R, K285I and K357T and two silent mutations at codon 389 and 401. Mutational analysis is recommended to identify patients at risk of disease progression. Therefore, early detection of such mutations may allow timely treatment intervention to prevent or overcome resistance. Keywords: Chronic Myeloid Leukaemia; BCR-ABL kinase domain; imatinib resistance mutation.