title: DNMT3A intragenic hypomethylation is associated with adverse prognosis in acute myeloid leukemia.
abstract: DNA methyltransferase 3A (DNMT3A), a member of de novo methyltransferases, has been found with overexpression in several cancers including acute myeloid leukemia (AML). The present study was aimed to investigate the methylation status of DNMT3A intragenic differentially methylated region 2 (DMR2) using real-time quantitative methylation-specific PCR (RQ-MSP) and analyze its clinical significance in AML. Aberrant hypomethylation of DNMT3A gene was found in 55.3% (84/152) of AML cases, but the status of DNMT3A hypomethylation was not correlated with the expression of four DNMT3A isoforms as well as DNMT3A mutation. There was no significant difference in the rates of complete remission (CR) between patients with and without DNMT3A hypomethylation. However, the patients with DNMT3A hypomethylation had shorter overall survival (OS) time than those without DNMT3A hypomethylation (7 months vs. 11 months, P=0.034). Moreover, the patients with DNMT3A hypomethylation also showed significantly shorter OS than those without DNMT3A hypomethylation in cytogenetically normal AML (CN-AML) (7 months vs. 25 months, P=0.011). Multivariate analysis confirmed the independent adverse impact of DNMT3A hypomethylation in CN-AML. Our data suggest that DNMT3A DMR2 hypomethylation is a negative prognostic hallmark in CN-AML.
authors.affiliation: Department of Hematology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Ying-ying
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: Laboratory Center, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Dong-ming
authors.initials: DM
authors.lastname: Yao
authors.affiliation: Department of Hematology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Xiao-wen
authors.initials: XW
authors.lastname: Zhu
authors.affiliation: Department of Hematology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Jing-dong
authors.initials: JD
authors.lastname: Zhou
authors.affiliation: Laboratory Center, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Ji-chun
authors.initials: JC
authors.lastname: Ma
authors.affiliation: Department of Hematology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Laboratory Center, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Xiang-mei
authors.initials: XM
authors.lastname: Wen
authors.affiliation: Laboratory Center, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Guo
authors.affiliation: Laboratory Center, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China. Electronic address: linjiangmail@sina.com.
authors.forename: Jiang
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Hematology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China. Electronic address: qianjun0007@hotmail.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Qian
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D000090205:DNA Methyltransferase 3A; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction; D055815:Young Adult
chemical_list: C000717967:DNMT3A protein, human; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A
keywords: Acute myeloid leukemia; DNMT3A; Hypomethylation