伊马替尼治疗后慢性粒细胞白血病患者BCR-ABL酪氨酸激酶区突变特征分析  

Characteristics of BCR-ABL tyrosine kinase domain point mutations in imatinib treated chronic myeloid leukemia patients

作　　者：王慧睿[1] 郭淑利[1] 李波[1] 王万里[1] 王松云[1] 肖蓬莉 田红旗[1] 

机构地区：[1]郑州大学附属洛阳中心医院血液内科,河南洛阳471009

出　　处：《新乡医学院学报》2017年第6期489-492,共4页Journal of Xinxiang Medical University

摘　　要：目的研究伊马替尼治疗的慢性粒细胞白血病(CML)患者BCR-ABL酪氨酸激酶区点突变发生情况。方法对伊马替尼治疗的30例CML患者的37份骨髓标本采用巢式反转录-聚合酶链式反应进行反转录、扩增、测序;应用Gene Bank进行序列同源性比较,分析BCR-ABL酪氨酸激酶区点突变发生情况,并分析其与伊马替尼耐药的关系。结果 30例患者检出突变10例,阳性率33.3%。10例突变患者共检出9种点突变,分别为T315I 2例、E255K1例、D276G+F317L 1例、F317L 2例、Y253H+M244V 1例、F359V 1例、H396R 1例、E279K 1例。CML-加速/急变期(AP/BP)、CML-慢性期(CP)患者的突变检出率分别为38.5%(5/13)和29.4%(5/17),CML-AP/BP患者突变检出率与CML-CP患者比较差异无统计学意义(χ~2=1.258,P>0.05);10例点突变患者中7例检出点突变时疾病进展至AP/BP,3例患者检出点突变时仍处于CP;AP/BP患者检出点突变的中位时间为6个月,明显早于CP患者的20个月(χ~2=9.103,P<0.05)。结论 BCR-ABL酪氨酸激酶区点突变是伊马替尼治疗CML失败的主要原因之一,定期监测BCR-ABL酪氨酸激酶区突变有助于酪氨酸激酶抑制剂疗效的评估和治疗方案的调整。Objective To explore the BCR-ABL tyrosine kinase domain point mutations in imatinib treated chronic myeloid leukemia（CML） patients.Methods Totally 37 bone samples from 30 CML patients were included in this study.All samples were reversely transcribed,amplified and sequenced by nested reverse transcription-polymerase chain reaction （RTPCR）;then the sequence homology was analysed by GeneBank.The occurrence of BCR-ABL tyrosine kinase domain point mutations was analysed and its relationship with imatinib resistance was analyzed.Results In the 30 patients,mutations in BCRABL kinase domain were detected in 10 patients（33.3%）.Nine types of mutations were detected,including T315I in two patients,E255K in one patient,D276G and F317L in one patient,F317L in two patients,Y253H and M244V in one patient,F359V in one patient,H396R in one patient,E279K in one patient.The mutation rate of patients with CML in the stage of accelerated-phase/blast-phase （AP/BP） and chronic-phase （CP） was 38.5% （5/13） and 29.4% （5/17） respectively,and there was no significant difference in the mutation rate between the two phase （x2 =1.258,P 〉 0.05）.In the ten patients,seven patients progressed to AP/BP when the mutation was detected,another three patients were still at CP.The median time of detection of mutation was 6 months in patients at the stage of AP/BP,which was significantly earlier than that in the patients at the stage of CP（20 months） （x2 =9.103,P 〈 0.05）.Conclusions BCR-ABL kinase domain mutation is one of the main reasons of imatinib resistance.Regular monitoring of BCR-ABL tyrosine kinase domain mutation is helpful in assessing the efficacy of tyrosine kinase inhibitors （TKI） in treatment of CML and adjusting the therapeutic regimens.

关 键 词：伊马替尼 慢性粒细胞白血病 酪氨酸激酶区 点突变 

分 类 号：R733.72[医药卫生—肿瘤]