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Gene Expression and Methylation Pattern in Hrk Apoptotic Gene in Myelodysplastic Syndrome



Zaker F1, 2 ; Amirizadeh N3 ; Nasiri N2 ; Razavi SM4 ; Teimooritoolabi L5 ; Yaghmaie M6 ; Mehrasa R3
Authors
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Authors Affiliations
  1. 1. Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Hematology, School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
  3. 3. Blood transfusion research center, High institute for Education, Research in Transfusion Medicine, Tehran, Iran
  4. 4. Hematology and Oncology Department, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran
  5. 5. Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
  6. 6. Hematology, Oncology and Stem cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran

Source: International Journal of Molecular and Cellular Medicine Published:2016

Abstract

Myelodysplastic syndromes (MDSs) are a clonal bone marrow (BM) disease characterized by ineffective hematopoiesis, dysplastic maturation and progression to acute myeloid leukemia (AML). Methylation silencing of HRK has been found in several human malignancies. In this study, we explored the association of HRK methylation status with its expression, clinical parameters and MDS subtypes in MDS patients. To study the methylation status of HRK gene, we applied Methylation Sensitive-High Resolution Melting Curve Analysis (MS-HRM) in MDS patients, as well as healthy controls and EpiTect®PCR Control DNA. Real time RT-PCR was used for gene expression analysis. Methylation frequency in promoter region of HRK in patient samples was 20.37%. Methylation of HRK was significantly related to transcriptional downregulation (P = 0.023). The difference in frequency of hypermethylated HRK gene was significant between good (10%) and poor (71.42%) cytogenetic risk groups (P= 0.001), advanced stage MDS patients (66.66%) in comparison with early stage MDS patients (2.56%) (P = 0.00), higher- risk MDS group (61.53%) and lower- risk MDS group (7.31%) (P= 0.00). HRK hypermethylation was associated with advanced- stage MDS and downregulation of HRK gene may play a role in the progression of MDS.