Document Type : Original Article
Authors
1
Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
2
Department of Hematology, School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
3
Blood transfusion research center, High institute for Education and Research in Transfusion Medicine, Tehran, Iran
4
Hematology and Oncology Department, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran
5
Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
6
Hematology, Oncology and Stem cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran
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.
Keywords