Epigenetic DNA changes in childhood acute lymphoblastic leukemia - the drug treatment effect.

Abstract

The active DNA demethylation process may be linked with aberrant methylation and may be involved in leukemogenesis. We investigated the role of epigenetic DNA modifications in childhood acute lymphoblastic leukemia (ALL) development. We analyzed the levels of 5-methyl-2′-deoxycytidine (5-mdC) oxidation products in the cellular DNA and urine of children with ALL (at diagnosis and after completion of chemotherapy, n=55) using two-dimensional ultra-performance liquid chromatography with tandem mass spectrometry (2D UPLC–MS/MS). Moreover, the expression of Ten Eleven Translocation enzymes (TETs) at the mRNA and protein levels was determined. Additionally, the ascorbate level in blood plasma was analyzed. Before treatment, the ALL patients had profoundly higher levels of the analyzed modified DNA in their urine than the controls. After chemotherapy, we observed a statistically significant decrease in active demethylation products in urine, with the final level similar to the level characteristic of healthy children. The level of 5-hmdC on the DNA of the blood leukocytes in the patient group was significantly lower than it was in the control group. Our data suggest that urinary excretion of epigenetic DNA modification may be a marker of pediatric ALL pathogenesis and a reliable marker of chemotherapy response.