Thiopurine methyltransferase polymorphisms and mercaptopurine tolerance in Turkish children with acute lymphoblastic leukemia (original) (raw)

2011, Cancer Chemotherapy and Pharmacology

Purpose Thiopurine methyltransferase (TPMT) enzyme is involved in the metabolism of 6-mercaptopurine (6-MP), a key component of acute lymphoblastic leukemia (ALL) treatment protocols in children. The aims of this study were to investigate the frequency of common genetic polymorphisms associated with low TPMT activity and correlations of polymorphic variants with 6-MP tolerance in a group of Turkish children with ALL. Methods Genotyping for G238C, A719G, and G460A mutations were performed by using NanoChip Technology. Adverse reactions during the Wrst 6 months of maintenance therapy with oral 6-MP and methotrexate were retrospectively analyzed from patient's Wles. Results Five (8.6%) of 58 children with ALL had a polymorphic TPMT allele: 4 (3.4%) were heterozygous for TPMT*3A (G460A and A719G), and one (0.9%) was heterozygous for TPMT*3C (A719G). No cases with TPMT*3B (G460A) or TPMT*2 (G238C) variants were identiWed. Children with TPMT*3A and *3C had signiWcantly lower leukocyte and neutrophil counts and percentage of target 6-MP dosage, and longer periods with ¸grade 2 infections, ¸grade 2 liver toxicity, and chemotherapy interruptions than the children with wild-type TPMT during the Wrst 24 weeks of maintenance therapy.