采用逆转录病毒技术建立人慢性粒细胞性白血病小鼠模型
发布时间：2018-09-09 20:41
【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。
[Abstract]:Chronic myeloid leukemia (Chronic Myeloid Leukemia (CML) is a malignant clonal proliferative disease originating from pluripotent hematopoietic stem cells. It is characterized by the significant increase and infiltration of late myelocytes in peripheral blood bone marrow and extramedullary organs. The course of chronic myeloid leukemia is usually divided into three stages, namely, chronic (chronic phase CP); accelerated (accelerate phase AP) and sudden change (blast crisis BC). Previous studies have shown that the establishment of CML model can deepen our understanding of the pathophysiological process of CML and its pathogenetic molecular mechanism. At present, the successful method is to establish CML mouse model by using retrovirus-infected mouse bone marrow cells combined with bone marrow transplantation. We packaged high titer viral particles using retrovirus technology, combined with mouse hematopoietic stem progenitor cell transplantation, induced BCR/ABL fusion protein expression in mouse hematopoietic stem progenitor cells, and the transplanted mice developed disease from 19 to 25 days. It was characterized by proliferation of mature granulocytes in peripheral blood and bone marrow, obvious enlargement of liver and spleen, destruction of normal structure of medulla of hepatic lobule and spleen, and infiltration of a large number of granulocytes. The expression of Gr-1,Mac-1 in spleen and bone marrow cells of the infected mice was significantly higher than that in the control group by flow cytometry, which was similar to the human CML like lesion. Results the mouse model of human chronic myeloid leukemia was successfully established by retrovirus technique. This provides a platform for us to further study the pathogenesis of CML, disease progression and the function of screening new therapeutic drugs and other oncogenes.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R733.7;R-332
本文编号：2233516
[Abstract]:Chronic myeloid leukemia (Chronic Myeloid Leukemia (CML) is a malignant clonal proliferative disease originating from pluripotent hematopoietic stem cells. It is characterized by the significant increase and infiltration of late myelocytes in peripheral blood bone marrow and extramedullary organs. The course of chronic myeloid leukemia is usually divided into three stages, namely, chronic (chronic phase CP); accelerated (accelerate phase AP) and sudden change (blast crisis BC). Previous studies have shown that the establishment of CML model can deepen our understanding of the pathophysiological process of CML and its pathogenetic molecular mechanism. At present, the successful method is to establish CML mouse model by using retrovirus-infected mouse bone marrow cells combined with bone marrow transplantation. We packaged high titer viral particles using retrovirus technology, combined with mouse hematopoietic stem progenitor cell transplantation, induced BCR/ABL fusion protein expression in mouse hematopoietic stem progenitor cells, and the transplanted mice developed disease from 19 to 25 days. It was characterized by proliferation of mature granulocytes in peripheral blood and bone marrow, obvious enlargement of liver and spleen, destruction of normal structure of medulla of hepatic lobule and spleen, and infiltration of a large number of granulocytes. The expression of Gr-1,Mac-1 in spleen and bone marrow cells of the infected mice was significantly higher than that in the control group by flow cytometry, which was similar to the human CML like lesion. Results the mouse model of human chronic myeloid leukemia was successfully established by retrovirus technique. This provides a platform for us to further study the pathogenesis of CML, disease progression and the function of screening new therapeutic drugs and other oncogenes.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R733.7;R-332
【参考文献】
相关期刊论文 前2条
1 朱磊;郭静明;;慢性粒细胞白血病的治疗进展[J];航空航天医药;2010年08期
2 刘伟,季明春,李厚达;人慢性粒细胞白血病动物模型研究进展[J];中国比较医学杂志;2005年01期
，本文编号：2233516
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