Personalized Therapy with Mercaptopurine in Acute Lymphoblastic Leukemia: Current Advances and Challenges

Mercaptopurine (6-MP) is a cornerstone drug for acute lymphoblastic leukemia (ALL) maintenance therapy. As a prodrug and purine analog, 6-MP is converted into the active cytotoxic product through a series of metabolic processes in the body. Its cytotoxic effects are mediated by the overactivation of deoxyribonucleic acid (DNA) mismatch repair mechanisms. The metabolism of 6-MP is influenced by multiple enzymes, and genetic polymorphisms encoding these enzymes affect drug tolerance and adverse reactions. Owing to significant individual variability, therapeutic drug monitoring (TDM) during 6-MP therapy has gained increasing attention, although no consensus has yet been established. Therefore, optimizing 6-MP maintenance regimens to mitigate adverse reactions and increase efficacy during this phase is critically important. Currently viable strategies include thiopurine enhanced ALL therapy (TEAM) and combination therapy with allopurinol. Finally, the issue of 6-MP resistance is attracting attention. Identifying methods for early detection of acquired resistance and developing corresponding strategies is important for improving the prognosis of ALL patients.