BCR-ABL Mutation Detection in Thai Chronic Myeloid Leukemia Patients

Tharinee Iadthong, Nittaya Limsuwanachot, Saengsuree Jootar, Pimjai Niparuck, Budsaba Rerkamnuaychoke

Abstract


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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