摘要
目的检测骨髓增生异常综合征(MDS)患者骨髓RASSF1A基因的表达水平及其启动子区甲基化状态,探讨RASSF1A基因异常甲基化在MDS发生发展中的作用,为去甲基化药物治疗MDS提供新靶点。方法选取30例MDS患者为实验组,非恶性血液病患者15例为对照组,按MDS国际IPSS评分标准对实验组进行分组。应用甲基化特异性聚合酶链反应(MS PCR)、逆转录PCR(RT PCR)法检测两组患者骨髓RASSF1A基因mRNA表达水平及启动子区甲基化状态,对比地西他滨治疗前后的MDS患者RASSF1A基因的甲基化情况。结果实验组RASSF1A基因甲基化率(73.33%)明显高于对照组(P<0.05),且中高危MDS患者骨髓RASSF1A基因甲基化率(81.8%)明显高于低危MDS患者(18.2%)(P<0.05);实验组RASSF1A基因mRNA表达水平明显低于对照组(P<0.05);经地西他滨治疗后,MDS患者RASSF1A基因的甲基化程度较初诊时降低。结论 MDS患者骨髓RASSF1A基因的异常甲基化与该基因的表达失活紧密相关,可能是MDS发生发展的机制之一;地西他滨能够逆转RASSF1A基因的甲基化,为地西他滨治疗MDS提供新的理论依据。
Objective To examine the expression level of RASSF1A gene and the methylation status of its promoter region in bone marrow of patients with myelodysplastic syndromes （MDS）, and to explore the correlation between RASSF1A gene methylation pathogenesis and development of MDS, in order to provide a new target for demethylation drugs. Methods 30 patients with MDS were chosen as the study group and 15 patients with non-malignant hematological diseases were chosen as the control group. Divide the study group according to the MDS IPSS risk score. Methylation specific PCR（ MS PCR） was employed to detect the methylation status of the RASSF1A gene promoter region in the 30 patients with MDS. Expression levels of RASSF1A mRNA were also determined by reverse transcription PCR （RT PCR）. Contrast the RASSF1A methylation status of the MDS patients before and after using Decitabine. Results The RASSF1A methylation rate of the study group （73.33%） was much higher than that of the control group（P 〈0. 05 ）, and the RASSF1A methylation rate of the medium-high risk MDS patients（ 81.8% ） is obviously higher than that of the low-risk MDS patients （ 18.2% ） （ P 〈 0.05 ） ; Meanwhile, the RASSF1A mRNA expression level of the study group was significantly lower than that of the control group（ P 〈 0.05 ）. The RASSF1A methylation level of the MDS patient after Decitabine treatment was lower than that of newly diagnosed patients. Conclusion A significant correlation existed between RASSF1A hypermethylation and the loss of expression of RASSF1A mRNA in MDS. The hypermethylationof the RASSF1A gene promoter region may be one of the mechanisms related to the pathogenesis of MDS. Decitabine can reduce the methylation levels in the RASSF1A gene and it also provides a new theoretical basis for using Decitabine as the treatment of MDS.
出处
《山东大学学报（医学版）》
CAS
北大核心
2013年第2期65-69,共5页
Journal of Shandong University:Health Sciences
基金
山东省科技厅项目(Y2006C63)
