title: Epigenetic dysregulation ofNKD2is a valuable predictor assessing treatment outcome in acute myeloid leukemia.
abstract: AIM:The present study was aimed to investigateNKD2expression as well as promoter methylation and further analyze their clinical significance in patients with acute myeloid leukemia (AML).METHODS:Real-time quantitative PCR was carried out to detect the pattern ofNKD2expression in 113 AML patients and 24 controls. Real-time quantitative methylation-specific PCR (RQ-MSP) and bisulfite sequencing PCR (BSP) were carried out to detectNKD2promoter methylation in 101 AML patients and 24 controls with available DNA.RESULTS:The level ofNKD2transcript in AML patients was significantly down-regulated as compared with controls (P=0.039).NKD2methylation level in AML patients was significantly higher than controls (P=0.044). Moreover,NKD2methylation negatively correlated withNKD2expression in AML patients (R=-0.218,P=0.029). Furthermore, demethylation ofNKD2could increaseNKD2expression in the leukemic cell line THP1 (P<0.05).NKD2low-expressed and high-expressed patients showed no statistical significance in complete remission (CR) rate among cytogenetically normal AML (CN-AML). However, lowNKD2expression was associated with shorter overall survival (OS) time and acted as independent risk factor in CN-AML according to Kaplan-Meier (P=0.029) and Cox regression analyses (P=0.022). Furthermore, gene expression (GEP) data also confirmed the prognostic value ofNKD2expression in CN-AML patients. Moreover,NKD2showed significantly increased level in post-CR than initial diagnosis in follow-up AML patients (P=0.024).CONCLUSION:DecreasedNKD2expression inactivated by promoter hypermethylation is a common event in AML and is associated with adverse outcome in CN-AML patients.
authors.affiliation: Department of Hematology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Xi-Xi
authors.initials: XX
authors.lastname: Li
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: Department of Hematology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Ting-Juan
authors.initials: TJ
authors.lastname: Zhang
authors.affiliation: Department of Hematology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Lei
authors.initials: L
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: 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: Department of Hematology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Zhi-Hui
authors.initials: ZH
authors.lastname: Zhang
authors.affiliation: Laboratory Center, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
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.
authors.forename: Jun
authors.initials: J
authors.lastname: Qian
keywords: NKD2; acute myeloid leukemia.; expression; methylation; prognosis