title: Tumor suppressor gene BLU is frequently downregulated by promoter hypermethylation in myelodysplastic syndrome.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Hematology, The Sixth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Jiaotong University, Shanghai, People's Republic of China.
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Yang
authors.forename: Qingxia
authors.initials: Q
authors.lastname: Zhang
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.forename: Lingyun
authors.initials: L
authors.lastname: Wu
authors.forename: Qi
authors.initials: Q
authors.lastname: He
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003598:Cytoskeletal Proteins; D019175:DNA Methylation / Q000502:physiology*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D003598:Cytoskeletal Proteins; D025521:Tumor Suppressor Proteins; C472720:ZMYND10 protein, human