Aberrant Methylation-Mediated Suppression of Apaf1 in Myelodysplastic Syndrome



Zaker F^{1, 2} ; Nasiri N² ; Amirizadeh N³ ; Razavi SM⁴ ; Yaghmaie M⁵ ; Teimooritoolabi L⁶ ; Maleki A⁷ ; Bakhshayesh M¹
Source: International Journal of Hematology-Oncology and Stem Cell Research Published:2017

Abstract

Background: 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 (TSG),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 clinicopathological factors in myelodysplastic syndrome (MDS) patients. Materials and Methods: Methylation Sensitive-High Resolution Melting Curve Analysis (MS-HRM) was employed in studying the methylation of CpG islands in the APAF1promoter region in MDS. Gene expression was analyzed by using real time RT-PCR. Results: 42.6% of patient samples were methylated in promoter region of APAF1 analyzed, while methylation of the genewas not seen in controls (P<0.05). Methylation of APAF1 was significantly associated with the suppression of its mRNA expression (P=0.00). The methylation status of APAF1in 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 (69.2%) compared to lower-risk MDS group (34.14%) (P=0.026). Conclusion: Our study indicated that APAF1hypermethylation in MDS was associated to high-risk disease classified according to the IPSS, WHO and cytogenetic risk. © 2017, Tehran University of Medical Sciences (TUMS). All rights reserved.