Thiopurine S-Methyltransferase Pharmacogenetics in Childhood Acute Lymphoblastic Leukemia
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Pharmacogenetics is the growing field of study of genetic variations underlying interindividual differences in drug response. Inherited polymorphisms in genes coding for drug-metabolizing enzymes, transporters, and targets influence toxicity as well as efficacy associated with the medication. Thiopurines are agents widely used in hematologic malignancies, transplantation, and chronic inflammatory conditions. Myelosuppression is the commonly encountered dose-limiting toxicity. Polymorphisms in the thiopurine S-methyltransferase gene (TPMT ), the predominant inactivating enzyme for thiopurines in hematopoietic tissue, are correlated with enzymatic activity of TPMT, thiopurine metabolism, and risk of clinical toxicity. In this chapter, we present TPMT genotype assessment that allows for prescribing pharmacogenetically guided doses to enhance patient safety and drug efficacy.
