A small proportion of patients with acute lymphoblastic leukemia (ALL) may experience severe leukopenia after treating with 6-mercaptopurine (6MP), which can be largely explained by germline variants in TPMT and NUDT15. However, a minority of patients who suffered such adverse drug reaction have NUDT15wt/wtTPMTwt/wt genotype, indicating that other genetic factors may take part in. Here, TPMT is linked to acute lymphoblastic leukemia.