Genetic polymorphism and thiopurine methyltransferase activity in acute lymphoblastic leukemia children

Thiopurine methyltransferase (TPMT, EC.2.1.1.67) is a cytoplasmic enzyme that catalyzes the S-methylation of aromatic and heterocyclic sufhydyl compounds such as 6-mercaptopurine. TPMT activity is regulated by a common genetic polymorphism that is associated with large individual variation in thiopurine toxicity and efficacy. Population studied has shown trimodal of frequency distribution TPMT activity in Caucasian. However, the mutant alleles of TPMT have interethnic variability with different frequency and pattern among various ethnic population. In the present investigation, genetic polymorphism and thiopurine methyltransferase activity were studied in 90 children of acute lymphoblastic leukemia. The erythrocyte thiopurine methyltransferase activity was measured by high-performance liquid chromatography (HPLC) technique. The mutant alleles, TPMT*2, TPMT*3A, and TPMT*3C, were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). TPMT activity has shown bimodal frequency distribution with the high and intermediate metabolizers of 93.33% and 6.67% respectively. The mutant allele was found only TPMT*3C. Gender had no effect on TPMT activity, however receiving 6-MP increased TPMT activity.