title: DDX43 promoter is frequently hypomethylated and may predict a favorable outcome in acute myeloid leukemia.
abstract: DEAD box polypeptide 43 (DDX43), a cancer/testis antigen (CTA), has been found to be overexpressed in various solid tumors and some hematologic malignancies. In the present work hypomethylation of the DDX43 gene was detected in 15% (32/214) of primary acute myeloid leukemia (AML) using real-time quantitative methylation-specific PCR (RQ-MSP). The level of DDX43 expression was correlated with DDX43 hypomethylation (R=0.277, P=0.014). Moreover, bisulfite sequencing confirmed the significant correlation between the methylation density and the level of DDX43 hypomethylation. Additionally, restoration of DDX43 expression in the K562 cell line by 5-aza-2'-deoxycytidine treatment confirmed a direct contribution of methylation in regulating the DDX43 gene. DDX43 hypomethylation was observed more frequently in favorable group (21.4%) and intermediate group (15.8%) than in poor group (0%) (P=0.009). AML patients with DDX43 hypomethylation had a better overall survival (median not obtained) than those with DDX43 methylation (median 8 months, 95% confidence interval 5.6-10.4 months) (P=0.014). In summary, the DDX43 gene is activated by promoter hypomethylation and DDX43 hypomethylation may be a favorable prognostic factor in AML.
authors.affiliation: Laboratory Center, Affiliated People's Hospital of Jiangsu University, Zhenjiang, People's Republic of China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Lin
authors.affiliation: Laboratory Center, Affiliated People's Hospital of Jiangsu University, Zhenjiang, People's Republic of China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Haematology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Haematology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, People's Republic of China. Electronic address: qianjun0007@hotmail.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Qian
authors.affiliation: Laboratory Center, Affiliated People's Hospital of Jiangsu University, Zhenjiang, People's Republic of China.
authors.forename: Zhao-qun
authors.initials: ZQ
authors.lastname: Deng
authors.affiliation: Laboratory Center, Affiliated People's Hospital of Jiangsu University, Zhenjiang, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Qian
authors.affiliation: Department of Haematology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, People's Republic of China.
authors.forename: Xing-xing
authors.initials: XX
authors.lastname: Chen
authors.affiliation: Laboratory Center, Affiliated People's Hospital of Jiangsu University, Zhenjiang, People's Republic of China.
authors.forename: Ji-chun
authors.initials: JC
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC, Tianjin, People's Republic of China.
authors.forename: Dong-sheng
authors.initials: DS
authors.lastname: Xiong
authors.affiliation: Department of Haematology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, People's Republic of China.
authors.forename: Yu-juan
authors.initials: YJ
authors.lastname: Ma
authors.affiliation: Department of Haematology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, People's Republic of China.
authors.forename: Cui
authors.initials: C
authors.lastname: An
authors.affiliation: Department of Haematology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, People's Republic of China.
authors.forename: Chun-yan
authors.initials: CY
authors.lastname: Tang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D059785:Karyotype; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic; D055815:Young Adult
chemical_list: D009363:Neoplasm Proteins; C412324:DDX43 protein, human; D053487:DEAD-box RNA Helicases
keywords: Acute myeloid leukemia; DDX43; Hypomethylation; Prognosis