Analysis of ABL kinase domain mutation in chronic myeloid leukemia patients resistant to imatinib

Objective To analyze the mutations of ABL tyrosine kinase in chronic myeloid leukemia(CML) patients who were resistant to imatinib.Methods A total of 56 bone marrow samples from the patients resistant to imatinib were analyzed by nested polymerase chain reaction to amplify ABL kinase domain,followed by direct sequencing and sequence homologous analysis.Results Among the 56 samples analyzed,ABL domain mutations were found in 17 samples which included 14 point mutations and 3 insertion mutations.The point mutations presented with 8 types of nucleotide changes,namely T315I,N358D,F359V,T389A,P441L,E450K,S410G and F486S.All the 3 insertion mutations were c.1423-1424ins 35bp(p.C475YfsX11).Among the 17 mutations,the number of cases in chronic phase(CP),accelerated phase(AP) and blast phase(BP) was 12,4 and 1,respectively.The incidences of mutation in both AP and BP of CML were higher than that in CP.Conclusion ABL kinase point mutation may be an important mechanism for imatinib resistance.The detection of ABL kinase point mutations should be helpful to estimate the prognosis and adjust the therapeutic strategy.