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

ABSTRACT: 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 NUDT15 ^wt/wt TPMT ^wt/wt 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 NUDT15 (rs116855232, P = 6.4 × 10^-11) and TPMT (rs1142345, P = 0.003), a novel variant

SUBMITTER: Cao M 

PROVIDER: S-EPMC7098961 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature