PH阳性白血病ABL激酶区基因多态性探究.pdfVIP

目 录 （三号黑体，居中） 1 PH 阳性白血病ABL 激酶区基因多态性研究„„„„„„„1 1.1 中文摘要„„„„„„„„„„„„„„„„„„„„„1 1.2 英文摘要„„„„„„„„„„„„„„„„„„„„„3 1.3 前言„„„„„„„„„„„„„„„„„„„„„„„5 1.4 材料与方法„„„„„„„„„„„„„„„„„„„„7 1.5 结果„„„„„„„„„„„„„„„„„„„„„„„12 1.6 讨论„„„„„„„„„„„„„„„„„„„„„„„24 1.7 结论„„„„„„„„„„„„„„„„„„„„„„„30 1.8 参考文献„„„„„„„„„„„„„„„„„„„„„31 1.9 英汉缩略词对照表„„„„„„„„„„„„„„„„„35 2 致谢„„„„„„„„„„„„„„„„„„„„„„„36 3 伊马替尼治疗ph 阳性白血病研究进展 （综述） „„„„„„„„„„„„„„„„„„„„„„„„„39 （四号宋体） PH 阳性白血病ABL 激酶区基因多态性研究 摘 要 （三号黑体，居中） 目的：检测白血病患者外周血或骨髓单个核细胞 BCR-ABL 基因的表达情 况，并探讨BCR-ABL 基因表达的临床意义。探讨ph 阳性白血病患者ABL 激酶区点突变发生情况，及在伊马替尼耐药患者中的意义。 方法：1 应用SYBR Green Ⅰ实时定量RT-PCR 法（RQ-PCR ）检测 例 PH 白血病患者BCR-ABL mRNA 表达情况，并对其临床特征与BCR-ABL 基因表达水平进行相关性分析。2 利用荧光免疫杂交技术对的骨髓标本进 行BCR-ABL 基因的检测。3 应用巢式RT-PCR 对患者不同时期的骨髓或血 液标本进行ABL 激酶区扩增，对产物进行纯化、测序以及序列同源性比对， 确定点突变的存在和类型。 结论：白血病患者BCR-ABL mRNA 表达阳性，但表达水平低于 人，两组基因定量 比较值RQ 为 。诱导化疗获得CR 后 表达水平较治疗前 治疗前后两者定量 比较值RQ 为 差异具有统计学意义（p ）, BCR-ABL 基因表达水平与患者性别，年 龄，外周血白细胞计数，骨髓中幼稚细胞比例，有无相关性，与治疗反应有无相关性。 ABL 激酶区点突变是伊马替尼治疗ph+ 白血病失败的重要原因之一，发生 伊马替尼耐药的患者BCR-ABL 基因ABL 激酶区存在高频率的点突变，定 期检测ABL 激酶区点突变有助于早期采取干预措施，提高治疗水平，。 关键词： PH 染色体；ABL 激酶区；点突变； Abstract: PH chromosome positive leukemia gene polymorphism analysis bjective : To detect the patients with leukemia peripheral blood or bone marrow mononuclear cells the expression of the BCR-ABL gene, and to explore the clinical significance of BCR-ABL gene expression. Study of the pH positive leukemia patients with ABL kinase zone point mutation occurs, and the resistance to imatinib in patients Methods : 1SYBR Green application of real-time quantitative RT-PCR method ( RQ-PCR ) was detected in patients with PH BCR-ABL mRNA expression in patients with leukemia, a