Investigation methylation status of tumor suppressor gene NR4A1 and NR4A3 and frequency of rs1569686 polymorphism of DNMT3B gene in patients with acute myeloid leukemia

Document Type : Original article

Authors

1 Department of Hematology and Blood Banking, School of Allied Medical Sciences, Zanjan University of Medical Sciences, Zanjan, Iran

2 Cancer Gene Therapy Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.

3 Hematologic Malignancies Reserch Center, Research Institute for Oncology, Hematology and Cell Therapy, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

4 Department of Medical Biotechnology, School of Medical Sciences, Zanjan University of Medical Sciences, Zanjan, Iran

Abstract

Acute myeloid leukemia (AML) is the most frequent type of leukemia among adults. Investigating AML heterogeneity based on DNA methylation can improve clinical diagnosis and prognosis. This study was conducted to investigate NR4A1 and NR4A3 gene methylation in fifty newly diagnosed AML patients and fifty healthy controls using Methyl specific PCR (MSP). The frequency of the rs1569686 in the DNMT3B was also determined by Tetra primer ARMS PCR. Also, the association between methylation of studied genes and some prognostic marker including mutation of FLT3 and NPM genes, as well as some hematological factors of patients was evaluated. According to the findings, AML patients have a significantly higher prevalence of methylated NR4A1 and NR4A3 genes than those without AML. AML patients with un-methylated NR4A3 had significantly higher frequency of FLT-ITD positivity than AML patients with methylated NR4A3. Also, there was no significant association between rs1569686 and AML. Finally, the distribution of different genotypes of rs1569686 between AML patients with and without methylation in NR4A1 and NR4A3 did not show any significant association. The results found that NR4A1 and NR4A3 were hyper-methylated in AML patients. However, rs1569686 polymorphism was not a main contributor to methylation status of studied gene. Future studies should consider other mechanisms influencing the role of NR4A1 and NR4A3 hypermethylation in AML.

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