Altered expression of DNMT3A gene in B-cell acute lymphoblastic leukemia by mercaptopurine

Abstract

Introduction: Current medications used for acute lymphoblastic leukemia (ALL) such as mercaptopurine target molecular factors involved in its onset and progression including DNA methyltransferases (DNMTs) because these enzymes are implicated in methylation and therefore expression of genes which are related to cell proliferation. This study evaluated the effect of mercaptopurine on the DNMT3A gene expression. Materials and Methods: The study was an analytical study of before and after type, performed on 8 children with B-cell ALL referred to children’s medical center of Tehran enrolled by convenience sampling. Their blood samples were taken in pre-treatment phase as well as 2 months after treatment with mercaptopurine. Ten healthy children referred to Yazd central medical laboratory were also sampled. RNA was extracted from the blood samples, and DNMT3A gene expression was measured by reverse transcriptase polymerase chain reaction (RT-PCR). Results: DNMT3A gene expression in patients with B-cell ALL who received mercaptopurine was significantly higher compared with pre-treatment time (P < 0.05). Conclusion: Increased expression of this regulatory gene occurred due to drug mercaptopurine. So, the mechanism of action of this drug may be through epigenetic processes due to higher methylation of DNA in leukemic cells.

Keywords

• dnmt3a
• epigenesis
• gene expression
• leukemia
• lymphoid
• 6-mercaptopurine