Aberrant Promoter Hypermethylation of Mir34a and Mir200b Genes in Pediatric Acute Lymphoblastic Leukemia

Abstract

Background: Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Epigenetic factors especially DNA methylation of promoter associated cytosine connected to guanine by phosphodiester bond (CpG islands) are considered as one of the most effective mechanisms in pathogenesis of ALL and have been demonstrated as a biomarker for lineage and subtype classification, prognostication, and disease progression. Objectives: In the present study, we examined the relationship between the promoter hypermethylation of the mir-200b and mir-34a regulator genes on the Notch signaling pathway in patients with ALL and controls in order to investigate association between promoter hypermethylation and development, progression and clinical factors. Methods: Genomic DNA was extracted from 60 samples (30 blood samples from leukemia patients and 30 normal samples) and modified by sodium bisulfite. Methylation-specific PCR was used to analyze the promoter methylation status of mir-34a and mir200b genes in the studied population. The results were analyzed with SPSS software version 20. Results: Our results showed significant association of mir-200b (P < 0.0001) and mir-34a (P < 0.004) genes hypermethylation with ALL. Also there was significant relationship between hypermethylation of mir-200b gene with family history (P = 0.003) and platelets (P = 0.01), and methylation of mir-34a gene with cancer state (P = 0.003) and Hb (P = 0.001) in ALL. Conclusions: In this study, we emphasized the important role of epigenetics on acute lymphoblastic leukemia development and progression. Our results showed that analysis of the methylation status of mir200b and mir-34a genes can provide novel prognostic markers for ALL.