TPMT and leukemia: According to the established guideline, the thiopurine dose is pharmacogenetically titrated based on the known risk variants of NUDT15 and TPMT. However, a substantial proportion of patients with leukemia presenting no genetic variation in NUDT15 or TPMT still experience life-threatening toxicities, which may result in dose reduction and/or discontinuation of thiopurine, resulting in therapeutic failure and relapse of leukemia.