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

ABSTRACT: 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.

SUBMITTER: Li XX

PROVIDER: S-EPMC5332898 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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

Li Xi-Xi XX Zhou Jing-Dong JD Zhang Ting-Juan TJ Yang Lei L Wen Xiang-Mei XM Ma Ji-Chun JC Yang Jing J Zhang Zhi-Hui ZH Lin Jiang J Qian Jun J

Journal of Cancer 20170211 3

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 ...[more]

PMID: 28261348

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Project description:BACKGROUND:microRNA-381 is dysregulated in a variety of cancers. However, its clinical significance in pediatric acute myeloid leukemia (AML) is still unclear. The purpose of this study was to detect the expression level of miR-381 in pediatric AML patients and to explore its potential clinical significance. METHODS:The levels of miR-381 in bone marrow and serum of 102 pediatric AML patients were measured by quantitative real-time polymorperase chain reaction (qRT-PCR). The diagnostic value of serum miR-381 in pediatric AML patients was evaluated by the receiver operating characteristic (ROC) curve. A Chi square test was used to analyze the relationship between serum miR-381 and the clinical characteristics of patients. Cox regression analysis and Kaplan-Meier evaluated the prognostic value of serum miR-381 in patients. Finally, the proliferation of the cells was analyzed by the CCK-8 assay. RESULTS:Compared with healthy controls, the levels of miR-381 in serum and bone marrow of pediatric AML patients were significantly decreased (P?<?0.001). ROC curve showed that miR-381 could distinguish pediatric AML cases from normal controls. At the same time, the downregulation of miR-381 was associated with M7 in the French-American-British (FAB) classifications and unfavorable cytogenetic risks (P?<?0.05). Low serum miR-381 levels were associated with poor overall survival of pediatric AML (log-rank test, P?=?0.011) and poor relapse-free survival (log-rank test, P?=?0.004). Cox regression analysis confirmed that reduced serum miR-381 was an independent predictor of poor prognosis in AML (HR?=?3.794, 95% CI 1.3633-10.559, P?=?0.011). In addition, low expression of miR-381 significantly reduced the proliferation of cells (P?<?0.05). CONCLUSION:All experimental results confirm that miR-381 has reduced bone marrow and serum expression in pediatric AML, and low levels of serum miR-381 have certain diagnostic and prognostic value in pediatric AML and may be a potential therapeutic target for AML.

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

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Epigenetic dysregulation of <i>NKD2</i> is a valuable predictor assessing treatment outcome in acute myeloid leukemia.

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