title: Clinical implications of the quantitative detection of ID4 gene methylation in myelodysplastic syndrome.
abstract: BACKGROUND
  Myelodysplastic syndrome (MDS) eventually transforms into acute leukemia (AL) in about 30% of patients. Hypermethylation of the inhibitor of DNA binding 4 (ID4) gene may play an important role in the initiation and development of MDS and AL. The aim of this study was to quantitatively assess ID4 gene methylation in MDS and to establish if it could be an effective method of evaluating MDS disease progression.
  
  
  METHODS
  We examined 142 bone marrow samples from MDS patients, healthy donors and MDS-AL patients using bisulfite sequencing PCR and quantitative real-time methylation-specific PCR. The ID4 methylation rates and levels were assessed.
  
  
  RESULTS
  ID4 methylation occurred in 27 patients (27/100). ID4 gene methylation was more frequent and at higher levels in patients with advanced disease stages and in high-risk subgroups according to WHO (P < 0.001, P < 0.001, respectively) and International Prognostic Scoring System (IPSS) (P = 0.002, P = 0.007, respectively) classifications. ID4 methylation levels changed during disease progression. Both methylation rates and methylation levels were significantly different between healthy donor, MDS patients and patients with MDS-AL (P < 0.001, P < 0.001, respectively). Multivariate analysis indicated that the level of ID4 methylation was an independent factor influencing overall survival. Patients with MDS showed decreased survival time with increased ID4 methylation levels (P = 0.011, hazard ratio (HR) = 2.371). Patients with ID4 methylation had shorter survival time than those without ID4 methylation (P = 0.008).
  
  
  CONCLUSIONS
  Our findings suggest that ID4 gene methylation might be a new biomarker for MDS monitoring and the detection of minimal residual disease.
authors.affiliation: Department of Hematology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China. lifehope666@126.com.|Department of Clinical Tests, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China. lifehope666@126.com.
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Kang
authors.affiliation: Department of Hematology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China. wongxr@163.com.
authors.forename: Xinrong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Hematology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China. 13911864393@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Hematology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China. cenj@yeah.net.
authors.forename: Jian
authors.initials: J
authors.lastname: Cen
authors.affiliation: Department of Clinical Tests, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China. limianyang301@163.com.
authors.forename: Mianyang
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Hematology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China. wwpku2000@hotmail.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Hematology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China. wangnan2000200005@163.com.
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Hematology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China. yonghuililab@yahoo.com.cn.
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Hematology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China. liliwang7644@126.com.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Hematology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China. ylmedsci@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Yu
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D019175:DNA Methylation; D006801:Humans; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000235:genetics*
chemical_list: C490128:ID4 protein, human; D051796:Inhibitor of Differentiation Proteins