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Int J Mol Cell Med. 2016 Spring;5(2):90-9. Epub 2016 Jun 19.

Gene Expression and Methylation Pattern in HRK Apoptotic Gene in Myelodysplastic Syndrome.

Author information

1
Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.; Department of Hematology, School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran.
2
Blood transfusion research center, High institute for Education and Research in Transfusion Medicine, Tehran, Iran.
3
Department of Hematology, School of Allied Medicine, Iran University of Medical Sciences, 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:

HRK; High Resolution Melting (HRM); methylation; myelodysplastic syndrome

PMID:
27478805
PMCID:
PMC4947213

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