Currently, 6-MP dose is clinically titrated based on the known risk variants of TPMT or NUDT15. However, a substantial proportion of leukemia patients who have no genetic variation in NUDT15 or TPMT still suffer from life-threatening toxicity, which may result in dose reduction and/or discontinuation of 6-MP and resultant therapeutic failure and relapse. Here, NUDT15 is linked to leukemia.