title: [p15(INK4B) methylation on prognosis and response to decitabine in patients with MDS].
abstract: OBJECTIVE
  To detect p15(INK4B) methylation levels and the kinetics of the methylation status before and after decitabine to explore its influences on prognosis and response to decitabine in myelodysplastic syndromes (MDS) patients.
  
  
  METHODS
  We examined 261 MDS patients (143 male and 118 female) with the median age of 52 years (32-78). Of them, 172 cases were low-risk group (low-risk 104 cases, intermediate-1 68 cases), 89 cases high-risk group (intermediate-2 52 cases, high risk 37 cases). Collections of bone marrow mononuclear cells of MDS patients and extracted the genomic DNA, the methylation status of p15(INK4B) was detected by methylation-specific PCR (MSP) method. Survival analysis was conducted according to the level of p15(INK4B) methylation in the cohort of patients. The kinetics of the methylation levels of p15(INK4B) in 58 MDS patients before and after 2 courses of decitabine have been assessed with the method of MSP.
  
  
  RESULTS
  The methylation level of p15(INK4B) in low-risk group patients was significantly lower than that in high-risk group (117.22 vs 157.63, P<0.05 ). The expected 2-year survival rate of p15(INK4B) methylation positive patients was lower than that of negative ones (91.8% vs 69.8%, P<0.05); the expected 2-year survival rate of p15(INK4B) methylation positive patients was shorter than that of negative ones in low-risk group（78.2% vs 92.0%, P<0.05）, meanwhile there was no significant difference in terms of expected 2-year survival rate and median expected survival between p15(INK4B) methylation positive and negative patients in high-risk group [35.6% vs 38.5%, (17.0±9.3) month vs (18.0±5.7) month, P>0.05]. Multivariate analysis showed p15(INK4B) methylation degree was an independent prognostic factor for overall survival. No statistical difference of overall response (OR) rates were found between p15(INK4B) methylation positive patients and negative patients before decitabine（65.9% vs 76.5%, P>0.05）, and complete remission (CR) rates between these two groups also showed no statistical difference（22.0% vs 29.4%, P>0.05）. p15(INK4B) methylation levels had no obvious change before and after treatment in decitabine responders（P>0.05）.
  
  
  CONCLUSIONS
  The survival of newly diagnosed MDS patients with positive p15(INK4B) methylation was comparatively shorter, but p15(INK4B) methylation had no influence on response to decitabine.
authors.affiliation: Department of Hematology, The Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lu-xi
authors.initials: LX
authors.lastname: Song
authors.forename: Ling-yun
authors.initials: LY
authors.lastname: Wu
authors.forename: Chun-kang
authors.initials: CK
authors.lastname: Chang
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D001374:Azacitidine / Q000031:analogs & derivatives*; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics*; D019175:DNA Methylation; D000077209:Decitabine; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000235:genetics; D011379:Prognosis; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: C493966:CDKN2B protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15; D000077209:Decitabine; D001374:Azacitidine