title: [Study of aberrant p73 promoter methylation in patients with myelodysplastic syndrome].
abstract: OBJECTIVE
  To study the methylation status of p73 gene promoter in patients with myelodysplastic syndrome (MDS) and explore its significance with clinical prognosis.
  
  
  METHODS
  Methylation of p73 promoter was detected in bone marrow cells from 135 MDS patients and 13 healthy controls by methylation-specific PCR (MSP). The results of MSP were confirmed by bisulfite sequencing. The expression of p73 mRNA was detected by real-time quantitative PCR. Primary bone marrow cells from MDS patients were treated with decitabine, the changes of p73 methylation status and p73 mRNA expression were measured. The role of p73 methylation in the prognosis of MDS and the correlated clinical data were explored.
  
  
  RESULTS
  p73 hypermethylation was present in 37.04% of MDS cases and patients with high risk MDS (RAEB-1 and RAEB-2) exhibited a significantly higher frequency of p73 methylation than that of low risk MDS (58.8% vs 29.7%, P = 0.002). The expression of p73 mRNA in the methylated group was decreased compared to that of the unmethylated group (P = 0.032). Decitabine treatment decreased the level of p73 methylation and increased the level of p73 transcripts. Patients with p73 methylation progressed rapidly to AML (P < 0.001) and had shorter survival (P = 0.002) than those who did not have p73 methylation. In the multivariate Cox regression model, BM blast and p73 methylation status emerged as independent prognostic factor for overall survival and leukemia free survival.
  
  
  CONCLUSIONS
  p73 gene methylation is common in patients with MDS and may indicate poor prognosis. p73 may be a therapeutic target in MDS.
authors: Department of Hematology, Shanghai Jiaotong University, Shanghai, China.
authors: You-shan
authors: YS
authors: Zhao
authors: Rui
authors: R
authors: Yang
authors: Shu-cheng
authors: SC
authors: Gu
authors: Juan
authors: J
authors: Guo
authors: Xi
authors: X
authors: Zhang
authors: Ling-yun
authors: LY
authors: Wu
authors: Xiao
authors: X
authors: Li
authors: Chun-kang
authors: CK
authors: Chang
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins