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Objective: Considering the high incidence of acute lymphoblastic leukemia (ALL), it is necessary to research this illness and determine genetic markers associated with it. The role of DNMT I gene expression during treatment with mercaptopurine drugs in children with B-cell ALL (B-ALL) is important because its changes reflect the effectiveness or ineffectiveness of the drugs. We have investigated the effect of mercaptopurine drugs on DNMT I expression in children with B-ALL. Methods: This analytical study assessed 8 B-ALL children who referred to Tehran Children's Medical Center and 10 healthy children referred to the Yazd Central Laboratory by convenience selection in 2016. Blood samples were obtained before and after treatment, and extraction of total RNA from each sample was performed for realtime qPCR of the target gene (DNMT I). Simultaneously, we evaluated GAPDH, a housekeeping gene. Data from gene expressions were compared by the paired t-test, using SPSS-16 software. Results: DNMT I gene expression was significantly decreased after mercaptopurine administration in children with B-ALL (P<0.02). Conclusion: Our findings suggest that the mercaptopurine drug may affect DNMT I gene regulation. This epigenetic effect may explain the mechanism of drug action, possibly serve as a diagnostic factor, and a means of better monitoring for patients with ALL. [ABSTRACT FROM AUTHOR]