Gene polymorphisms in the folate metabolism and their association with MTX-related adverse events in the treatment of ALL

The antifolate drug methotrexate (MTX) is widely used in the treatment of various neoplastic diseases, including acute lymphoblastic leukemia (ALL). MTX significantly increases cure rates and improves patients' prognosis. Despite that it achieved remarkable clinical success, a large number of patients still suffer from treatment toxicities or side effects. Even to this date, chemotherapeutic regiments have not been personalized because of interindividual differences that affect MTX response, especially polymorphisms in key genes. The pharmacological pathway of MTX in cells is useful to identify gene polymorphisms that influence the process of treatment. The aim of this review was to discuss the gene polymorphisms of drug-metabolizing enzymes in the MTX pathway and their toxicities on ALL treatment.