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International Journal of Hematology-Oncology and Stem Cell Research، جلد ۲۰۱۵، شماره ۱۰، صفحات ۰-۰
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عنوان انگلیسی Aberrant promoter methylation pattern of apoptotic gene APAF1 in myelodysplastic syndrome patients
چکیده انگلیسی مقاله Objectives: Myelodysplastic syndromes (MDSs) include a diverse group of clonal bone marrow disorders characterized by ineffective hematopoiesis and pancytopenia. It was found that down regulation of APAF1 , a putative tumor suppressor gene, leads to resistance to chemotherapy and disease development in some cancers. In this study, we investigated the relation of APAF1 methylation status with its expression and clinicopathologic factors in myelodysplastic syndrome (MDS) patients. Methods: Methylation Sensitive-High Resolution Melting Curve Analysis (MS-HRM) was used to study the methylation pattern of APAF1 gene promoter in MDS patients. Gene expression was analyzed by using real time RT-PCR. Results: delta ct mean for APAF1 in patient and control groups was 2.8 and 1.6 respectively. 42.6% of the patient samples were methylated in the promoter region of APAF1 analyzed, while methylation of the gene was not seen in controls. Methylation of APAF1 was significantly associated with the suppression of its mRNA expression (p=0.00). In general, APAF1 methylation was significantly higher in the MDS patients compared with healthy controls (P< 0.05). The methylation status of APAF1 in advanced stage MDS patients (80%) was significantly higher than that of the early stage MDS patients (28.2%) (P=0.001). The difference in frequency of hypermethylated APAF1 gene was significant between good (37.5%) and poor (85.71%) cytogenetic risk groups (P=0.043). In addition, a higher frequency of APAF1 hypermethylation was observed in higher-risk MDS group (69.23%) compared to lower-risk MDS group (34.14%) (p=0.026). Conclusions: hypermethylation of APAF1 gene in MDS and suppression of its expression may contribute to the development of MDS.
کلیدواژه‌های انگلیسی مقاله HRM, Methylation, Myelodysplastic syndrome, APAF1
نویسندگان مقاله فرهاد ذاکر | farhad zaker


ناهید نصیری | nahid nasiri


ناصر امیری زاده | naser amirizadeh


سید محسن رضوی | seyed mohsen razavi


مرجان یغمایی | marjan yaghmaie


لادن تیموری طولابی | ladan teimoori toolabi


رویا مهرآسا | roya mehrasa


نشانی اینترنتی http://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/590
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