急性白血病细胞与正常白细胞差异蛋白质组分析

Analysis of the Different Proteomes between the Acute Leukemia Cells and Normal White Blood Cells

本研究利用蛋白质组学方法将急性白血病(acuteleukemia,AL)细胞与正常白细胞进行差异蛋白质组分析,为AL的分子诊断和白血病发生的分子机制研究奠定基础。利用二维凝胶电泳将40例AL患者的AL细胞和20例正常自愿者淋巴细胞、粒细胞的蛋白质进行分离,利用MALDI-TOF-MS生物质谱和电喷雾串联质谱(ESI-MS/MS)对差异表达的蛋白质进行鉴定分析。结果表明:在AL细胞与正常细胞的差异表达蛋白质中,一些与肿瘤的恶性转化(如Op18和NM23-H1)、细胞增殖(如PCNA)、抑制凋亡(如肿瘤坏死因子抑制蛋白)等相关的蛋白在AL细胞中高表达,而一些与正常白细胞分化和生理功能相关的蛋白质在AL细胞中低表达。结论:AL的发生涉及到众多的细胞事件,一些与恶性转化,细胞增殖和抑制凋亡等相关的蛋白在AL细胞中高表达,蛋白质组学分析为急性白血病发病的分子机理的解析提供了一个新的手段。

This study was aimed to analyze the different proteomes between human acute leukemia （AL） cells and normal white blood cells by proteomic technology in order to lay the basis for diagnosing AL and understanding the mechanism of leukemogenesis. The proteins from AL cells of 40 AL patients identified by FAB classification and proteins from normal lymphocytes and granulocytes of 20 normal volunteers were separated by two-dimensional electrophoresis （2-DE）, and the differentially expressed proteins between the two groups were identified by both matrix assisted laser desorption/ionization-time of flight-mass spectrometry （MALDI-TOF-MS） and electronspray ionization （ESI）-MS/MS. The results showed that among the differentially expressed proteins between AL cells and normal lymphocytes and granulocytes, some proteins involved in the process of malignant transformation （such as Op18, NM23-H1）, cell proliferation （ such as PCNA） and apoptosis inhibition （ such as tumor necrosis factor inhibitor protein） were found to be up regulated in AL cells. However, some proteins involved in differentiation and physiological functions of normal cells were down regulated in AL cells. It is concluded that there are many events involved in the process of leukemogenesis, expression of some proteins relating to the malignant transformation, cell proliferation and apoptosis inhibition are up- regulated in AL cells. The proteome analysis may provide a new approach to explaining the molecular mechanism underlying the pathogenesis of AL.