Examination of Point Mutations within the ABL Kinase Domain of Bcr-Abl Fusion Gene in Chinese Patients with Chronic Myeloid Leukemia Who Develop Imatinib Resistance.

Objective: To investigate the point mutations within the ABL kinase domain (KD) of Bcr-Abl fusion gene in Chinese patients with chronic myeloid leukemia who develop IM resistance and investigate the mutation.

Method: We collect a total of 17 bone marrow samples obtained from 11 patients who showed hematology resistance(n=7) or cytogenetic refractoriness(n=4). A long semi-nest PCR method was used to amplify the ABL KD of the Bcr-Abl fusion gene. After two cycles of PCR reaction, we get a fragment including 863 bases, purified and sequenced it.

Result: The ABL point mutation was detected in 45.45% of patients. The mutation rate of hematology resistance is 57.14% and the mutation rate of cytogenetic refractoriness is 25%. In total, we find three point mutation in all of our patients tested, ie, G250E(2), E255K(1) and T315I(2). In patients who develop hematology resistance, the earliest time to detect mutation is 4 months later after the therapy of IM and the longest time to detect mutation is 9 months later after the therapy of IM. In patients who develop cytogenetic refractoriness, the time to detect mutation is 12 months later after the therapy of IM .For the patients whose samples are available, no single mutation happens before IM thearpy.

Conclusion: There is high frequency of point mutations clustered within the adenosine triphosphate-binding region of Bcr-Abl fusion gene in Chinese patients with chronic myeloid leukemia, and the mutation is related to IM therapy. It’s good for patients to switch to another therapeutic strategy when the mutations were detected earlier.

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