【摘要】：慢性粒細(xì)胞白血病Chronic Myeloid Leukemia (CML)是起源于多能造血干細(xì)胞的惡性克隆增殖性疾病,以外周血、骨髓及髓外器官中中、晚幼粒細(xì)胞顯著增多、浸潤為特點。慢性粒細(xì)胞白血病病程通常分為三個階段,即慢性期(chronic phase CP);加速期(accelerate phase AP)及急變期(blast crisis BC)。已有的研究顯示建立CML模型可加深我們對CML病理生理過程的了解及對其致病分子機制的認(rèn)識。 目前較成功的方法是應(yīng)用逆轉(zhuǎn)錄病毒感染小鼠骨髓細(xì)胞聯(lián)合骨髓移植建立的CML小鼠模型。這里我們采用逆轉(zhuǎn)錄病毒技術(shù)包裝出了高滴度的病毒顆粒,結(jié)合小鼠造血干祖細(xì)胞移植技術(shù),誘導(dǎo)BCR/ABL融合蛋白在小鼠造血干祖細(xì)胞中表達,移植小鼠于19-25天發(fā)病,表現(xiàn)為外周血和骨髓中成熟粒細(xì)胞大量增生,肝臟,脾臟明顯腫大,肝小葉和脾臟的髓質(zhì)正常結(jié)構(gòu)破壞,并有大量粒細(xì)胞浸潤,流式細(xì)胞學(xué)分析發(fā)病小鼠脾臟及骨髓細(xì)胞Gr-1、Mac-1的表達均明顯高于對照組,類似于人CML樣病變。結(jié)果我們采用逆轉(zhuǎn)錄病毒技術(shù)成功建立了人慢性粒細(xì)胞性白血病小鼠模型。這為我們進一步研究慢粒發(fā)病機制、疾病演進過程以及篩選新的治療藥物和研究其它致癌基因的功能提供了平臺。
[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.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2011
【分類號】：R733.7;R-332

【參考文獻】

相關(guān)期刊論文 前2條

1 朱磊;郭靜明;;慢性粒細(xì)胞白血病的治療進展[J];航空航天醫(yī)藥;2010年08期

2 劉偉,季明春,李厚達;人慢性粒細(xì)胞白血病動物模型研究進展[J];中國比較醫(yī)學(xué)雜志;2005年01期

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