impact of oxidative stress and tpmt genetic variants on the pharmacodynamics of mercaptopurine in pediatric acute lymphoblastic leukemia

Acute lymphoblastic leukemia is the top malignancy in children, representing the largest portion of leukemia in childhood. 6- mercaptopurine (6-mp) is a part of the maintenance therapy aimed at having an additive effect with methotrexate in blocking purine synthesis and the growth of leukemic cells. this study investigates the relationship between tpmt genetic variations, oxidative stress markers such as malondialdehyde (mda), total antioxidant capacity (tac), and pharmacokinetics of 6-mp in pediatric all patients. blood samples were drawn from the participants before and after the treatment where mda, tac, complete blood count, hepatic enzymes were measured. the pcr sequencing of tpmt was also done for genotyping. for data analysis, the r statistical software was used. the mda level in the pediatric all patient group was 10.6 nmol/ml, interquartile range (iqr) 9-12 in contrast to the control group 2.4 nmol/ml, iqr 1.6-3.1, respectively, while tac was 0.43 mm/l, iqr 0.31-0.65 in patients and 1.5 mm/l, iqr 1.2-1.8 in control group which explains the increased oxidative stress. the mean hemoglobin levels were significantly reduced in patients (7.6 ±1.5 g/dl) as compared to control (12±0.7 g/dl) (p < 0.0001). similarly, mean platelet count was significantly reduced in patients (69 ± 24 ×10³/µl) as compared to normal controls (289 ± 68 ×10³/µl) (p < 0.0001). mean wbc count was found significantly low in patient's group (4.1 ×10³/µl) as compared. this study addresses the influence of tpmt polymorphisms and oxidation on the pk of 6-mp in paediatric all patients. the results suggest higher levels of free radicals, anemia, thrombocytopenia, and wbc variations in patients.