Relationship of the reduced folate carrier gene polymorphism G80A to methotrexate plasma concentration, toxicity, and disease outcome in childhood acute lymphoblastic leukemia.

摘要

Methotrexate (MTX) is a key agent in the che-motherapeutic regimens used in the treatment of childhood acute lymphoblastic leukemia (ALL). It is transported into the cell by the reduced folate carrier (RFC). A common polymorphism (G80A) in the second exon of the RFC1 gene results in amino acid substitution of arginine for histidine (H27R) in the first transmembrane domain, a region implicated in substrate binding and/or translocation. This substitution results in altered RFC transport properties and decreased RFC expression, and is correlated with altered MTX transport.