伊马替尼耐药CML患者ABL基因激酶区突变检测  

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

作　　者：宋其芳[1] 瞿燕春[2] 杨红宇[1] 王宏[1] 

机构地区：[1]暨南大学生命科学技术学院抗体工程研究中心,广州510632 [2]广东省中医院肿瘤科,广州510120

出　　处：《临床检验杂志》2011年第3期185-187,共3页Chinese Journal of Clinical Laboratory Science

基　　金：国家"863"专题项目(2009AA02Z112)

摘　　要：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17例,其中14例为点突变,包括T315I、N358D、F359V、T389A、P441L、E450K、S410G、F486S;3例检测出插入突变c.1423-1424ins 35bp(p.C475YfsX11)。慢性期患者突变12例(28.6%),加速期、急性期突变者分别为4例和1例。。IM急变期、加速期患者突变率高于慢性期,但差异无显著性(χ2=0.253,P>0.05)。结论 ABL基因激酶区点突变是CML患者对IM耐药的重要原因,通过检测ABL基因激酶区突变有助于预测IM疗效并及时调整治疗方案。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.

关 键 词：伊马替尼 慢性粒细胞白血病 突变 激酶区 

分 类 号：R733.72[医药卫生—肿瘤]