伊马替尼耐药CML患者ABL基因激酶区突变检测

目的 研究伊马替尼(imatinib,IM)治疗慢性粒细胞白血病(chronic myeloid leukemia,CML)耐药患者ABL酪氨酸激酶区突变情况.方法 用巢式PCR扩增对IM治疗耐药的56例CML患者骨髓样本ABL基因激酶区序列,通过测序和序列同源性检索分析ABL激酶区突变情况.结果 56例患者检出突变1...

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

Abstract: 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.