Paper Information

Journal:   INTERNATIONAL JOURNAL OF MOLECULAR AND CELLULAR MEDICINE   SPRING 2016 , Volume 5 , Number 2; Page(s) 90 To 99.
 
Paper: 

GENE EXPRESSION AND METHYLATION PATTERN IN HRK APOPTOTIC GENE IN MYELODYSPLASTIC SYNDROME

 
 
Author(s):  ZAKER FARHAD, AMIRIZADEH NASER, NASIRI NAHID*, RAZAVI SEYED MOHSEN, TEIMOORI TOOLABI LADAN, YAGHMAEI MARJAN, MEHRASA ROYA
 
* DEPT. OF HEMATOLOGY, SCHOOL OF ALLIED MEDICINE, IRAN UNIVERSITY OF MEDICAL SCIENCES, HEMMAT FREEWAY, 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 ofHRK 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 ofHRK 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 ofHRK in patient samples was 20.37%. Methylation ofHRK was significantly related to transcriptional downregulation (P=0.023). The difference in frequency of hypermethylatedHRK 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).
HRKhypermethylation was associated with advanced- stage MDS and downregulation of HRK gene may play a role in the progression of MDS.

 
Keyword(s): HIGH RESOLUTION MELTING (HRM), METHYLATION, MYELODYSPLASTIC SYNDROME, HRK
 
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