The Role of Pomalidomide-Based Epigenetic Effect on DNMT Genes Expression in Myeloma Cell Line

Abstract

Multiple myeloma (MM) is clonal B-cell malignancy characterized by the progressive proliferation of malignant plasma cells and accumulation of monoclonal immunoglobulin (M-spike) in blood and urine. Pomalidomide is an immunomodulatory agent which has potentially suppressed myeloma cell progression, especially in drug-resistant cases. As epigenetic modifications have an important role in gene regulation and because of the revealing role of DNA-Methyltransferase 1 (DNMT1) overexpression in myeloma pathogenesis, in this study DNMT1, 3a and 3b genes expression of U266 myeloma cell line treated with pomalidomide have been evaluated. In this study after treatment of U266 cells with 1 μM pomalidomide for 48 hours, total RNA extraction and cDNA synthesis was performed. Gene expression of DNMT1, 3a and 3b has been evaluated using real time PCR technique. The result of this study show that pomalidomide can downregulate the expression of DNMT1, 3a, and 3b in 48 hours of treatment as 0.049, 0.058 and 0.055, respectively as comparing with untreated control (P<0.05). Based on these results we conclude that pomalidomide has desired effect on epigenetic modification by downregulation of DNMTs genes expression and has been considered as an effective drug for inhibition of myeloma proliferation.

Keywords

• Multiple myeloma
• U266
• Pomalidomide
• DNA methyltransferase