成人急性髓性白血病SOCS-1基因及其甲基化的研究

The Methylation of SOCS-1 Gene in Adult Acute Myeloid Leukemia

目的:通过检测成人急性髓性白血病中SOCS-1基因表达水平及其甲基化水平,研究其在白血病发病中的作用。方法:运用甲基化特异性PCR(Methylation specific PCR,MSP)方法,对24例急性髓性白血病患者和4株白血病细胞株(Jurkat、Raji、U 937、NALM 17),进行SOCS-1基因甲基化水平的研究;同时运用Real-time PCR法定量分析SOCS-1基因表达水平。以10例健康人为正常对照组。结果:24例成人急性髓性白血病患者中,15例有SOCS-1基因甲基化(62.5%),而正常对照组无SOCS-1基因甲基化(0%),二者有显著差异(P<0.05);SOCS-1基因甲基化组与无SOCS-1基因甲基化组相比较,其SOCS-1基因相对表达量明显减少(P﹤0.05);与患者临床病理特征相结合比较,发现SOCS-1基因的甲基化与患者年龄、性别和病程阶段无相关。4株白血病细胞株中,Jurkat和U 937表现有SOCS-1甲基化(50%),Raji和NALM 17无SOCS-1甲基化,前者SOCS-1基因表达量较后者也明显降低(P<0.05)。结论:SOCS-1基因在成人急性髓性白血病中甲基化水平明显增高,且SOCS-1基因甲基化后表达水平受到抑制,提示SOCS-1基因及其甲基化在急性髓性白血病的发生发展中可能具有一定作用。

Objective： To investigate the role of SOCS-1 （Suppressor of Cytokine Signalling-l） in tumorigenesis of adult acute myeloid leukemia （AML）by detecting the methylation state and expression of SOCS-1 gene. Methods： A total of 24 patients with AML, 10 healthy volunteers and 4 cell lines （Jurkat, Raji, U 937, NALM 17） were chosen. The methylation state of SOCS-1 in samples and cell lines were detected by using methylation-specific polymerase chain reation （MSP）, and the expression of SOCS-1 was detected by using Real-time PCR. Results： The aberrant methylation of SOCS-1 was 62.5 % （ 15/24 ）in primary patients with AML. In contrast, there was no aberrant methylation of SOCS-1 gene in normal samples （P〈0.05）. The expression of SOCS-1 in AML patients with aberrant methylation of SOCS-1 gene was lower than that in AML patients without aberrant methylation of SOCS-1 gene （P〈0.05）. There was no relation between the methylation of SOCS-1 gene and the clinicopathological data （such as sex, age and tumor stage）. Conclusion： The methylation of SOCS-1 gene in AML was higher than that in control group significantly （P〈0.05）, and aberrant methylation strongly correlates with reduced expression. SOCS-1 gene may play an important role in tumorigenesis of AML.