Epigenetic dysregulation of NKD2 is a valuable predictor assessing treatment outcome in acute myeloid leukemia

AIM: The present study was aimed to investigate NKD2 expression 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 of NKD2 expression in 113 AML patients and 24 controls. Real-time quantitative methylation-specific PCR (RQ-MSP) and bisulfite sequencing PCR (BSP) were carried out to detect NKD2 promoter methylation in 101 AML patients and 24 controls with available DNA. RESULTS: The level of NKD2 transcript in AML patients was significantly down-regulated as compared with controls (P=0.039). NKD2 methylation level in AML patients was significantly higher than controls (P=0.044). Moreover, NKD2 methylation negatively correlated with NKD2 expression in AML patients (R=-0.218, P=0.029). Furthermore, demethylation of NKD2 could increase NKD2 expression in the leukemic cell line THP1 (P<0.05). NKD2 low-expressed and high-expressed patients showed no statistical significance in complete remission (CR) rate among cytogenetically normal AML (CN-AML). However, low NKD2 expression 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 of NKD2 expression in CN-AML patients. Moreover, NKD2 showed significantly increased level in post-CR than initial diagnosis in follow-up AML patients (P=0.024). CONCLUSION: Decreased NKD2 expression inactivated by promoter hypermethylation is a common event in AML and is associated with adverse outcome in CN-AML patients.