RhoA和CDC42在急性白血病的表达异常及其意义

Expression of Rho GTPase family member RhoA and CDC42 protein in patients with acute leukemia

目的 检测急性白血病（AL）患者骨髓单个核细胞中RhoA和CDC42蛋白的表达水平,探讨Rho GTP酶相关的骨髓微环境与造血干细胞相互作用异常在白血病细胞恶性行为中的作用.方法 分离并制备54例AL患者及22名正常供者的骨髓单个核细胞的细胞裂解液,应用Western blotting方法,检测其中RhoA和CDC42蛋白的相对表达量,非配对t检验分析RhoA和CDC42蛋白在AL患者和正常供者中表达的差异,Spearman分析患者RhoA和CDC42基因的蛋白表达量与临床资料的相关性.结果 初治AL患者骨髓中RhoA和CDC42的蛋白表达水平显著高于健康人,其中急性髓系白血病M2、M3,及M5亚型患者的RhoA蛋白表达升高尤为显著,M3亚型患者的CDC42蛋白表达量升高最为显著.结论 初治AL患者骨髓中RhoA和CDC42表达显著上调,提示Rho GTP酶介导的白血病细胞迁移活跃导致骨髓微环境相互作用异常在白血病发生中起作用.

Abstract：Objective To detect the proteins levels of RhoA and CDC42 in bone marrow mononucleated cells （BMMC） of patients with primary acute leukemia,and further determine the role of abnormal interactions between hematopoietic progenitor and bone marrow microenvironment on abnormal behaviors of leukemia cells. Methods BMMC samples were separated from 54 primary acute leukemia patients and 22 normal donors and the cell lysis samples were prepared. RhoA and CDC42 proteins were determined by Western blotting. Independent pair T test was conducted to evaluate whether the differences in RhoA and CDC42 expression were statistically significant between leukemia patients and normal donors. Spearman was applied in analyzing the correlation between expression of RhoA and CDC42 proteins and clinical characters of patients. Results RhoA and CDC42 proteins level of primary acute leukemia patients was significantly higher than that of normal samples. Especially, patients with M2,M3 and M5 subtypes exhibited significant higher RhoA proteins levels and M3 subtype exhibited significant higher CDC42 protein levels. Conclusion RhoA and CDC42 protein levels of primary acute leukemia patients are significantly higher than that of normal donors. This result suggests that RhoA and CDC42 associated efficient migration of leukemia cells could be implicated in abnormal interaction of leukemic cell with bone marrow microenvironment.