BCR-ABL Mutation Detection in Thai Chronic Myeloid Leukemia Patients
Mutations in the kinase domain (KD) of BCR-ABL lead to drug resistance by
reducing the capacity of imatinib to inhibit kinase activity. The early detection of such
mutation may allow timely treatment intervention to prevent or overcome the resistance.
The objective of this report is to develop a direct sequencing method for detection of
BCR-ABL mutations in imatinib mesylate resistance CML patients. The detection method
involved RT-PCR amplification of the entire kinase domain of the BCR-ABL and then
detected all BCR-ABL point mutation by direct sequencing.
Twenty-nine cases of 59 CML patients (49.15%) were reported for the incidence
of BCR-ABL mutations. Multiple mutations were detected in 10.34 % of the patients
and the most frequently detected mutations were T315I and F359V for 13.56% each.
Moreover, the detected mutations were G250E, Y253H, Q252H, F359C, Y253F, E275K,
and F317L for 7 cases (11.86%), 6 cases (10.17%), 2 cases (3.39%), 2 cases (3.39%),
1 case (1.69%), 1 case (1.69%), 1 case (1.69%), respectively.
For summary, direct sequencing of the BCR-ABL kinase domain allowed detection
of emerging mutations and was able to detect mutations for a broad range of
BCR-ABL kinase domain exon 4 to 9 in CML patients.
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