关键词: 基因;RASSF1A;DNA甲基化;CpG岛; 骨髓增生异常综合征

Abstract:

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 hypermethylation of 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.

Key words: Gene； RASSF1A； DNA methylation； CpG island； Myelodysplastic syndrome