间期荧光原位杂交结合测序分析在慢性髓系白血病慢性期伊马替尼治疗监测中的应用  

Application of interphase fluorescence in situ hybridization and sequencing analysis in imatinib treatment of patients with chronic myeloid leukemia in chronic phase

作　　者：张嵩[1] 杜庆锋[2] 刘晓力[1] 欧阳昭[1] 刘志[1] 

机构地区：[1]南方医科大学南方医院血液科,广东广州510515 [2]南方医科大学南方医院临床医学教育中心,广东广州510515

出　　处：《第四军医大学学报》2009年第16期1515-1517,共3页Journal of the Fourth Military Medical University

基　　金：广州市科技攻关重点引导项目(2006Z3-E0401)

摘　　要：目的:探讨在慢性髓系白血病(CML)慢性期伊马替尼治疗中,间期荧光原位杂交(I-FISH)结合Abl酪氨酸激酶区测序技术对疗效监测、耐药分析及预后判断的意义.方法:应用双色双融合探针I-FISH对18例伊马替尼治疗获完全细胞遗传学缓解的CML慢性期患者骨髓内残留肿瘤细胞负荷进行检测,并对I-FISH检测阳性患者进行ABL酪氨酸激酶区测序分析.结果:双色双融合探针I-FISH的正常分界值为0.73%,18例伊马替尼治疗后患者检测中,8/18(44%)结果阳性;8例I-FISH检测阳性患者测序分析发现2例(25%)出现ABL激酶区点突变,点突变类型为E255K和T315I.结论:联合应用I-FISH和测序分析不仅能较灵敏、特异地监测伊马替尼治疗后肿瘤细胞负荷的变化,并可对药物疗效、耐药情况进行早期分析,有效地指导治疗和判断预后.AIM： To explore the significance of interphase fluorescence in situ hybridization （I-FISH） and sequencing analysis in evaluating the curative effect, drug resistance and prognosis of imatinib treatment for patients with chronic myeloid leukemia （CML） in chronic phase （CP）. METHODS： The tumor load was detected in 18 CML-CP cases with complete cytogenetic remission （CCR） , who were treated with imatinib by dual-color and dual-fusion r-FISH （ D-FISH ）. The point mutation of Abl kinase domain was analyzed in the patients with positive result of D-FISH by sequencing. RESULTS： In normal control, the cutoff rate of D-FISH was 0. 73%. The positive rate of D-FISH was 8/18 （44%） and 2 point mutations （E255K and T315I） of Abl kinase domain were found in 2 cases respectively. CONCLUSION ： Combination of I-FISH and sequencing analysis can be used as a sensitive and specific tool not only to monitor the tumor load in CML, but also to evaluate the curative effect, drug resistance and prognosis of imatinib treatment.

关 键 词：白血病 髓样 慢性 伊马替尼 原位杂交 荧光 点突变 

分 类 号：R733[医药卫生—肿瘤]