【摘要】 目的:通过对慢性粒细胞白血病(chronic myeloid leukemia,CML)患者骨髓细胞中错配修复基因(mismatch repair,MMR)h MSH2的表达水平及其调控机制的分析,探讨h MSH2与慢性粒细胞白血病疾病进展的联系。方法:用实时定量PCR方法检测10例对照,27例CML患者(包括慢性期9例,进展期8例,急变期10例)骨髓中4个MMR基因(h MSH2、h MSH6、h MLHl、h PMS2)m RNA的表达;用MSP方法检测MMR基因启动子区甲基化水平;用Western blot方法观察MMR蛋白水平在各组之间的差异。结果:与正常对照比较,CML患者的h MSH2的表达明显降低(P<0.05),其表达随疾病恶化而下降,依次为急变期<加速期<慢性期,而h MLHl、h PMS2、h MSH6的表达却未见异常;27例CML患者中出现3例h MSH2启动子区高甲基化。结论:CML患者的h MSH2表达水平比正常人显著降低,且随着疾病恶化其表达水平逐下降,提示h MSH2可能与CML疾病进展相关。更多还原

【Abstract】 Objective: To investigate the expression and regulation mechanism of mismatch repair(MMR) gene h MSh2 of bone marrow in chronic myeloid leukemia(CML), and study the relationship of mismatch repair gene h MSH2 and chronic myeloid leukemia progression. Methods: Expression of MMR genes h MSH2, h MSH6, h MLHl and h PMS2 m RNAs in 27 CML patients(including chronic phase 9, accelerated phase 8 and blast crisis 10 cases) and the normal control group(10 cases) were detected by quantitative polymerase chain reaction(Q-PCR); methyl-specific PCR(MSP) was used to analyze methylation status of h MLH1 and h MSH2 promoters in CML;the expression of h MSH2 protein was detected by Western blot. Results: The expression of h MSH2 was significantly lower in CML than in normal control(P <0.05), and decreased gradually with the deterioration of disease(blast crisis<accelerated phase<chronic phase), but there was no statistical significance in the expression of h MSH6, h MLHl and h PMS2 between CML and the control groups. In addition,h MSH2 promoter hypermethylation existed in 3 of 27 CML patients. Conclusion: Expression of h MSH2 was significantly lower in CML than in the control group and showed a gradual decline according to CML progress, which indicated that h MSH2 might be correlated with CML progress.更多还原