Screening of Novel Pharmacogenetic Candidates for Mercaptopurine-Induced Toxicity in Patients With Acute Lymphoblastic Leukemia

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 and . However, a minority of patients who suffered such adverse drug reaction have genotype, indicating that other genetic factors may take part in. In this study, we genotyped 539 exon-located nonsilent pharmacogenetic variants in genes involved in phase I/II of drug metabolism in 173 pediatric patients with ALL and conducted association screening for 6MP-induced leukopenia. Besides (rs116855232, = 6.4 × 10 ) and (rs1142345, = 0.003), a novel variant was identified in gene (i.e., rs73032311, = 0.0007), which is independent of variant. In addition, a variant (i.e., rs4680) in COMT is significantly associated with 6MP-induced hepatotoxicity ( = 0.007). In conclusion, variants in and may be considered as novel potential pharmacogenetic markers for 6MP-induced toxicities, but additional independent validations with large sample size and investigations on related mechanisms are further needed.