【作者】 李婧；

【导师】 潘宏铭；

【作者基本信息】 浙江大学 ， 肿瘤学， 2011， 硕士

【摘要】 慢性粒细胞白血病Chronic Myeloid Leukemia (CML)是起源于多能造血干细胞的恶性克隆增殖性疾病,以外周血、骨髓及髓外器官中中、晚幼粒细胞显著增多、浸润为特点。慢性粒细胞白血病病程通常分为三个阶段,即慢性期(chronic phase CP);加速期(accelerate phase AP)及急变期(blast crisis BC)。已有的研究显示建立CML模型可加深我们对CML病理生理过程的了解及对其致病分子机制的认识。目前较成功的方法是应用逆转录病毒感染小鼠骨髓细胞联合骨髓移植建立的CML小鼠模型。这里我们采用逆转录病毒技术包装出了高滴度的病毒颗粒,结合小鼠造血干祖细胞移植技术,诱导BCR/ABL融合蛋白在小鼠造血干祖细胞中表达,移植小鼠于19-25天发病,表现为外周血和骨髓中成熟粒细胞大量增生,肝脏,脾脏明显肿大,肝小叶和脾脏的髓质正常结构破坏,并有大量粒细胞浸润,流式细胞学分析发病小鼠脾脏及骨髓细胞Gr-1、Mac-1的表达均明显高于对照组,类似于人CML样病变。结果我们采用逆转录病毒技术成功建立了人慢性粒细胞性白血病小鼠模型。这为我们进一步研究慢粒发病机制、疾病演进过程以及筛选新的治疗药物和研究其它致癌基因的功能提供了平台。更多还原

【Abstract】 CML, a clonal disease of hematopoietic stem cells (HSCs) harboring CML-specific oncogenic fusion product BCR-ABL, displays a relatively benign clinical manifestation at chronic phase (CP), being caused mainly by a gross expansion of terminally differentiated neutrophils. Over several years, nevertheless, this relative indolent disease will progress, often through a transient period of accelerated phase (AP), ending up with the fatal stage of clinical course-blast crisis (BC). Models of chronic myeloid leukemia(CML) have proven invaluable for furthering of understanding of the molecular pathophysiology of this disease.A successful strategy is retroviral transduction of BCR/ABL into mouse bone marrow in vitro, followed by transplantation into syngeneic recipient mice. Here We have packaged high titer of virus particles and successfully induced CML in mice through transfecting mice hematopoietic stem cells with BCR-ABL expressing virus and transplanting to the same lineage recipients.Mouses were sacrificed at various time points between 19 and 25 days post bone marrow transplantation (BMT), they had extensive spleen, liver and BM involvement by the myeloproliferative process, Immunophenotyping of the involved tissues showed that the spleen, and BM contained significant numbers of myeloid (Gr-1+, Mac-1+) cells. These mice were similar to human CML. As a result we have successfully set up mouse model of CML by retroviral transduction of BCR/ABL into mouse bone marrow in vitro. Animal models of CML provide a technique platform for us to study the pathogenesis and process of CML, screen new drug and the function of other genes.更多还原