Epigenetic regulation of the "peroxisome proliferator activated receptor-gamma" gene in acute myeloid leukemia patients

Abstract

Objective: Peroxisome proliferator activated receptor gamma (PPAR) is a member of the nuclear hormone receptor family that regulates cellular growth, differentiation and apoptosis. PPAR gamma expression is present in normal bone marrow and peripheral CD34+ cells. There are studies showing that this regulation is decreased in acute myeloblastic leukemia (AML). However, there is no study of whether this reduction is transcriptional or epigenetic. For this purpose we investigated the expression and methylation levels of the PPAR gamma gene in AML and healthy control group. Material and Methods: Thirty-one newly diagnosed cases of AML and 25 healthy individuals were included in the study. Differences in the PPAR gamma gene expression between the study group and the control group were analyzed by real time polymerase chain reaction (RT-PCR) technique. Methylation-specific PCR was performed using the Epitect bisulfite protocol. After primers were designed, bisulfite DNA transformation was performed. The methylation level of the PPAR gamma gene was measured by the Epitect HRM PCR protocol. Results: As a result of RT-PCR, the expression of PPAR gamma gene in AML cases was found to be reduced by about 1.5 times compared to healthy individuals. When the methylation status of the PPAR gamma promoter region was examined by methylation-specific PCR in the cases where the PPAR gamma expression was decreased, methylation in the candidate gene region in AML cases was significantly increased (29% in AML cases and 8% in control group, p<0.001). Conclusion: In our study, the expression of the PPAR gamma gene was significantly reduced in patients with AML. It has also been shown that over-methylation of the promoter region may be responsible for suppression of this gene expression. © 2019 by Türkiye Klinikleri.