The Malaysian journal of pathology · 2024
Identification of novel BCR::ABL1 kinase domain mutation in patients with chronic myeloid leukaemia and imatinib resistance.
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Yusoff Y M, Seman Z A, Anoar S Z, Said S S M, Azman N, Kamaluddin N R, Abdullah J, Yacob S S M, Esa E
Аннотация
INTRODUCTION: The emergence of mutations in the BCR::ABL1 kinase domain (KD) impairs imatinib mesylate (IM) binding capacity, thus contributing to IM resistance. Identification of these mutations is important for treatment decisions and precision medicine in chronic myeloid leukaemia (CML) patients. Our study aims to determine the frequency of BCR::ABL1 KD mutations in CML patients with IM resistance.
MATERIALS AND METHODS: Twenty three CML patients (26.7%) showed to have BCR:ABL1 KD mutations with IM resistance.
RESULTS: A total of 14 different types of mutations were identified which are Y253H, E255K, T267A, A287T, M290R, F3111, T3151, F317L, F359V, F3591, F359C, K357T, A399T, E459K and two novel mutations; M290R and K357T. We also discovered two silent mutations at codons 389 and 401.
CONCLUSION: 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.
MATERIALS AND METHODS: Twenty three CML patients (26.7%) showed to have BCR:ABL1 KD mutations with IM resistance.
RESULTS: A total of 14 different types of mutations were identified which are Y253H, E255K, T267A, A287T, M290R, F3111, T3151, F317L, F359V, F3591, F359C, K357T, A399T, E459K and two novel mutations; M290R and K357T. We also discovered two silent mutations at codons 389 and 401.
CONCLUSION: 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.