Detection of ABL Kinase Domain Point Mutations in Chronic Myeloid Leukemia Patients Receiving Imatinib Treatment
2010
This study was purposed to evaluate ABL tyrosine kinase point mutations in imatinib-treated chronic myeloid leukemia(CML) patients and thier clinical significance.51 bone marrow samples from 28 imatinib-resistant patients and 10 newly diagnosed CML patients were collected.ABL kinase domain of bcr-abl allele was amplified by nested reverse transcription-polymerase chain reaction,followed by purifying,directly sequencing and sequence homology analysis of amplified products in order to determine the existence and type of point mutation.The results showed that the point mutations were found in 12 of 38 patients,and all the 12 ones progressed to advanced disease or death.2 patients showed Met351Thr mutation,7 patients showed Glu252His,2 patients showed Glu279Lys,the other types were Glu255Val and Glu355Gly,each of which was tested in one patient.The incidence of the point mutation was 17.6%,45.5% and 44.4% in chronic,accelerated and blast phase respectively.The incidences of point mutatim in hematologically and genetically resistant patients were 50%(5/10)and 44.4%(8/18),and the 95% confidence interval(CI) was 12.3%-87.7% and 19%-69.9% respectively.It is concluded that ABL kinase point mutation is an important mechanism of imatinib resistance,monitoring the ABL kinase domain point mutation is helpful to estimating the prognosis and adjusting the therapeutic strategy.
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