Résumé
Polymorphisms in drug metabolizing enzymes, transporters and/or pharmacological targets of drugs may profoundly influence the dose-response relationship between individuals sometimes exacerbating the drug toxicity. Mercaptopurine [6-MP] is a pro drug that has been used for past 35 to 40 years in the treatment of various types of cancers especially acute lymphoblastic leukemia [ALL] of childhood. Thiopurine S-methyltransferase [TPMT] is a cytosolic enzyme that catalyzes it inactivation through methylation. It has been found that the activity of TPMT possesses genetic polymorphism, as an autosomal recessive trait. Continuous efforts of researchers and scientists to find out the molecular basis for altered activity of this enzyme now has been defined with various rapid and inexpensive assays especially allele specific polymerase chain reaction [AS-PCR] and restriction fragment length polymorphism [RFLP]. These assays are now internationally available for the four commonest signature TPMT variant alleles 2[*], 3A[*], 3B[*] and 3C[*]. Various studies on TPMT genotyping and phenotyping in patients using 6 MP demonstrated its close association with the risk of myelotoxicity. Alarmingly altered TPMT genotype may influence the risk of secondary malignancies also, including brain tumors and acute myelogenous leukemia. This review highlights the current approaches to improve the clinical impact of 6-MP in childhood ALL in context with polymorphic TPMT gene. Some of these investigations are entering routine clinical practice internationally but a lot of work is required in determining their optimal use in patients with ALL at our part of the world