title: Decreased 5-hydroxymethylcytosine levels are associated with TET2 mutation and unfavorable overall survival in myelodysplastic syndromes.
abstract: The clinical significance and mechanisms of TET2 are not well defined in myeloid malignancies. We detected TET2 mutations and assayed its catalyzing conversion product 5-hydroxymethylcytosine (5-hmC) in 61 Chinese patients with MDS. Ten patients were identified to have TET2 mutations (16.4%). 5-hmC levels in patients with MDS with TET2 mutations were significantly lower than in those without mutations, and CD34+ cells of patients with MDS exhibited a lower 5-hmC content than that of controls. TET2 expression and 5-hmC in patients with MDS with P15 methylation were both significantly lower than in those without P15 methylation. We did not observe a correlation between TET2 mutations and overall survival (OS) in MDS. Interestingly, we found that patients with MDS with higher 5-hmC levels or in lower risk groups of the Revised International Prognostic Scoring System (IPSS-R) had a longer overall survival, suggesting that 5-hmC levels may be a new molecular marker for prognostic assessment of MDS and that revised IPSS criteria are also applicable to the risk categories of Chinese patients with MDS.
authors: Division of Hematology, Institute of Molecular Hematology, The Second Xiang-Ya Hospital, Central South University , Changsha, Hunan , P. R. of China.
authors: Xiaoliu
authors: X
authors: Liu
authors: Guangsen
authors: G
authors: Zhang
authors: Yan
authors: Y
authors: Yi
authors: Le
authors: L
authors: Xiao
authors: Minfei
authors: M
authors: Pei
authors: Sufang
authors: S
authors: Liu
authors: Yunya
authors: Y
authors: Luo
authors: Haiying
authors: H
authors: Zhong
authors: Yunxiao
authors: Y
authors: Xu
authors: Wenli
authors: W
authors: Zheng
authors: Jiankai
authors: J
authors: Shen
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003596:Cytosine / Q000031:analogs & derivatives*; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D049308:Dioxygenases; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000378:metabolism / Q000401:mortality*; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine; D049308:Dioxygenases; C541081:TET2 protein, human