Pharmacogenetics of asparaginase in acute lymphoblastic leukemia

Asparaginase is a key component in leukemias and lymphomas treatment protocols and is suggested as a treatment for other malignancies in which an amino acid depletion strategy is indicated. Asparaginase intolerance is subject to inter-individual variability and can manifest as hypersensitivity reactions, pancreatitis, thrombosis, as well as metabolic abnormalities, and may affect treatment outcome. Pharmacogenetics aims at enhancing treatment efficacy and safety by better understanding the genetic basis of variability and its effect on the pharmacological responses. Many groups tried to tackle the pharmacogenetics of asparaginase but the potential implementation of such findings remains debatable. In this review, we highlight the most important findings reported in studies of the pharmacogenetics of asparaginase related complications and treatment outcome in acute lymphoblastic leukemia.