科研之友
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摘要
BLU methylation status was investigated in bone marrow mononuclear cells from newly diagnosed myelodysplastic syndrome (MDS) patients and patients who received 5-aza-2'-deoxycytidine (decitabine) treatment so as to determine the effect of BLU in the pathogenesis of MDS. @@@ Methylation-specific polymerase chain reaction and bisulfite sequencing were used to evaluate the methylation status of the promoter region of the BLU gene. BLU expression was investigated by using quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blot analysis. @@@ Hypermethylation in the promoter region of BLU was detected in 34 of 79 (43%) newly diagnosed MDS patient samples and was significantly correlated with the loss of BLU mRNA and protein expression. There was a statistically significant difference in methylation frequency between the refractory anemia/refractory anemia with ringed sideroblasts/5q-syndrome (RA/RARS/5q-) group and the refractory anemia with excess blasts-1/-2 (RAEB-1/RAEB-2) group. A higher frequency of hypermethylation was observed in the intermediate-2/high-risk group compared to the low-risk/intermediate-1-risk group. The demethylating agent decitabine could partly reverse hypermethylation and restore the expression of the BLU gene. @@@ BLU promoter hypermethylation frequently occurs in MDS cases, especially in higher risk MDS cases, and is significantly associated with the downregulated expression of BLU. BLU gene re-expression was induced in some MDS cases undergoing decitabine therapy. BLU may play a substantial role in the development and etiology of MDS.
- 出版日期2012-5
- 单位上海交通大学
