Promoter DNA Methylation Frequency and Clinicopathological Role of miR-129-2 Gene in Patients with Chronic Lymphocytic Leukemia

Abstract

Objectives: Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of apparently mature B-type lymphocytes in the lymphohematopoietic organs. Methylation in promoters of tumor suppressor genes is one of the mechanisms that causes blood malignancy. In this study, we evaluated the promoter DNA methylation status of miR-129-2 tumor suppressor gene and its association with clinical and laboratory parameters of patients with CLL. Methods: We studied the promoter DNA methylation frequency of the miR-129-2 gene in 50 patients with CLL and 50 healthy controls using methylation-specific polymerase chain reaction methods. Statistical analysis was performed using SPSS-18 software, and a p-value < 0.050 was considered statistically significant. Results: The frequency of promoter DNA methylation of the miR-129-2 gene was significantly higher in the CLL group compared with control group (38.0% vs. 0.0%, p < 0.001; χ² = 23.457). The promoter DNA methylation frequency of miR-129-2 gene was not significantly different between the two sexes (p =0.236). A significant but weak correlation was seen between the methylated state of the miR-129-2 gene and organomegaly (p =0.019, r = 0.330) as well as hemoglobin levels (p =0.020, r = -0.233). However, binary logistic regression analysis indicated organomegaly as the only clinical biomarker with a statistically significant association with the hypermethylated miR-129-2 gene state (p =0.046). Conclusions: The high frequency of promoter DNA methylation of the miR-129-2 gene in the CLL group compared to the control group, as well as its significant association with organomegaly, suggests the importance of this epigenetic biomarker in the pathogenesis and prognosis of CLL disease.

Keywords

• epigenesis
• genetic
• dna methylation
• leukemia
• lymphocytic
• chronic
• b-cell