1. DDX43 promoter is frequently hypomethylated and may predict a favorable outcome in acute myeloid leukemia
- Author
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Cui An, Yu-Juan Ma, Zhao-Qun Deng, Chun-yan Tang, Dongsheng Xiong, Jun Qian, Jing Yang, Ji-chun Ma, Jiang Lin, Wei Qian, Xing-xing Chen, and Qin Chen
- Subjects
Adult ,Male ,Cancer Research ,Adolescent ,Karyotype ,Bisulfite sequencing ,Biology ,DEAD-box RNA Helicases ,Young Adult ,Antigen ,medicine ,Humans ,Promoter Regions, Genetic ,Gene ,Aged ,Aged, 80 and over ,Myeloid leukemia ,Cancer ,Hematology ,Methylation ,DNA Methylation ,Middle Aged ,Prognosis ,medicine.disease ,Confidence interval ,Neoplasm Proteins ,Leukemia, Myeloid, Acute ,Oncology ,Mutation ,Immunology ,Cancer research ,Female ,K562 cells - 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.
- Published
- 2014