Methylation‐associated DOK1 and DOK2 down‐regulation: Potential biomarkers for predicting adverse prognosis in acute myeloid leukemia. Issue 9 (14th March 2018)

• Record Type: Journal Article
• Authors: He, Pin‐Fang; Xu, Zi‐Jun; Zhou, Jing‐Dong; Li, Xi‐Xi; Zhang, Wei; Wu, De‐Hong; Zhang, Zhi‐Hui; Lian, Xin‐Yue; Yao, Xin‐Yu; Deng, Zhao‐Qun; Lin, Jiang; Qian, Jun
• Is Part Of: Journal of cellular physiology. Volume 233:Issue 9(2018:Sep.)
• Page Start: 6604
• Page End: 6614
• Publication Date: 2018-03-14
• Subjects: acute myeloid leukemia -- DOK1 -- DOK2 -- expression -- methylation; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.26271
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract : DOK‐1 and DOK‐2 ( DOK1/2 ) are closely related members of downstream of tyrosine kinase ( DOK ) family genes, which are found to be frequently rearranged in several hematopoietic cancers. However, the clinical implications of DOK1 / 2 in acute myeloid leukemia (AML) remain largely unknown. To investigate the clinical significance, real‐time quantitative PCR (RQ‐PCR) was carried out to detect DOK1 / 2 expressions in 125 de novo AML patients and 28 healthy controls. Real‐time quantitative methylation‐specific PCR (RQ‐MSP) and bisulfite sequencing PCR (BSP) were applied to detect DOK1 / 2 methylation level and density. DOK1 / 2 expressions were significantly down‐regulated in AML patients. The promoters of DOK1/2 were highly hypermethylated and negatively correlated with DOK1/2 expressions in AML patients. In addition, we also confirmed that DOK1 / 2 expressions could be restored by DOK1/2 demethylation using 5‐aza‐2′‐deoxycytidine in leukemia cell line THP‐1. Survival analyses showed that low‐expressed DOK1 / 2 were associated with markedly shorter overall survival and leukemia free survival in both whole‐cohort AML and non‐M3 AML patients. Multivariate analyses further revealed that DOK1 / 2 were act as independent prognostic factors in AML patients. These findings indicate that decreased DOK1 / 2 expressions associated with their promoter hypermethylations predict adverse prognosis in AML. Abstract : Our study found that DOK1 and DOK2 expressions were significantly down‐regulated in AML patients, and decreased DOK1/2 expressions associated with their promoter hypermethylations predict adverse prognosis in AML.