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International Journal of Hematology-Oncology and Stem Cell Research، جلد ۱۱، شماره ۳، صفحات ۲۲۵-۲۳۱
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عنوان انگلیسی Aberrant Methylation of APAF-1 Gene in Acute Myeloid Leukemia Patients
چکیده انگلیسی مقاله Background: Acute myeloid leukemia (AML) is a heterogeneous clonal disorder characterized by immature myeloid cell proliferation and bone marrow failure. Various genetic and epigenetic factors have been found to be influential in such patients. Methylation silencing of APAF-1, a putative tumor suppressor gene (TSG), has been found in several human malignancies. In this study, we explored the association of APAF-1 methylation status with AML patients. Subjects and Methods: We studied the methylation status of APAF-1 gene in 101 AML patients and 50 healthy subjects as controls. Genomic DNA was extracted from leukocytes in peripheral blood or bone marrow and the methylation status of APAF-1 gene promoter was detectedusing methylation-specific PCR (MSP) method with specific methylated and unmethylated primers. Gene expression was analyzed using real time RT-PCR. Results: The prevalence of methylated (MM) and hemi-methylated (MU) CpG dinucleotides within the APAF-1 gene promoter of AML patients was 12 (11.9%) and 45 (44.6%), respectively, while no methylation was detected in the control samples (p < 0.001). Our results showed a higher frequency of methylated APAF1 in FLT3-ITD mutated cases(p=0.04). APAF1 mRNA expression was significantly lower in methylated cases compared with normal cases. Conclusion: The present study indicated the increased frequency of hypermethylation of APAF-1 gene promoter in AML patients. APAF-1 aberrant CpG island methylation was associated with transcriptional downregulation in AML patients. Therefore, promoter methylation of APAF-1 gene could be considered as an epigenetic factor that contributes to the development of AML.
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نویسندگان مقاله علی ملکی | ali maleki
department of hematology, school of allied medical sciences, tehran university of medical sciences, tehran, iran

سازمان اصلی تایید شده: دانشگاه علوم پزشکی تهران (Tehran university of medical sciences)

فاطمه نادعلی | fatemeh nadali
department of hematology, school of allied medical sciences, tehran university of medical sciences, tehran, iran

سازمان اصلی تایید شده: دانشگاه علوم پزشکی تهران (Tehran university of medical sciences)

رضا علی بخشی | reza alibakhshi
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

سازمان اصلی تایید شده: دانشگاه علوم پزشکی ایران (Iran university of medical sciences)

فرهاد ذاکر | farhad zaker
department of hematology, school of allied medicine, iran university of medical sciences, tehran, iran

سازمان اصلی تایید شده: دانشگاه علوم پزشکی ایران (Iran university of medical sciences)

ناهید نصیری | nahid nasiri
department of hematology, oncology, kermanshah university of medical sciences, kermanshah, iran

سازمان اصلی تایید شده: دانشگاه علوم پزشکی کرمانشاه (Kermanshah university of medical sciences)

مهرداد پاینده | mehrdad payandeh
hematology-oncology and stem cell transplantation research center, tehran university of medical sciences, tehran, iran

سازمان اصلی تایید شده: دانشگاه علوم پزشکی تهران (Tehran university of medical sciences)

بهرام چهاردولی | bahram chahardouli
department of hematology, school of allied medical sciences, tehran university of medical sciences, tehran, iran

سازمان اصلی تایید شده: دانشگاه علوم پزشکی تهران (Tehran university of medical sciences)

شهربانو رستمی | shahrbano rostami


نشانی اینترنتی http://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/713
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زبان مقاله منتشر شده en
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نوع مقاله منتشر شده Original Article(s)
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