title: Gene Expression and Methylation Pattern in HRK Apoptotic Gene in Myelodysplastic Syndrome.
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.
authors.affiliation: 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.
authors.forename: Farhad
authors.initials: F
authors.lastname: Zaker
authors.affiliation: Blood transfusion research center, High institute for Education and Research in Transfusion Medicine, Tehran, Iran.
authors.forename: Naser
authors.initials: N
authors.lastname: Amirizadeh
authors.affiliation: Department of Hematology, School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Nahid
authors.initials: N
authors.lastname: Nasiri
authors.affiliation: Hematology and Oncology Department, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Seyed Mohsen
authors.initials: SM
authors.lastname: Razavi
authors.affiliation: Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Ladan
authors.initials: L
authors.lastname: Teimoori-Toolabi
authors.affiliation: Hematology, Oncology and Stem cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Marjan
authors.initials: M
authors.lastname: Yaghmaie
authors.affiliation: Blood transfusion research center, High institute for Education and Research in Transfusion Medicine, Tehran, Iran.
authors.forename: Roya
authors.initials: R
authors.lastname: Mehrasa
keywords: HRK; High Resolution Melting (HRM); methylation; myelodysplastic syndrome