Influence of methotrexate on purine and pyrimidine pools and on cell phase distribution of cultured human lymphoblasts.

Methotrexate (MTX) and 6-mercaptopurine (6MP) are among the most commonly used agents in the maintenance treatment of acute lymphoblastic leukemia (ALL) in children.1-3 There are biochemical considerations for an increased efficacy of a combination of both drugs in maintenance therapy of ALL. MTX is a strong inhibitor of dihydrofolate reductase. As a result tetrahydrofolates are reduced. Tetrahydrofolate coenzymes are required for one-carbon transfer reactions in purine de novo synthesis and thymidine biosynthesis. As a consequence a purine-less and a thymidy-late-less state will occur, ultimately resulting in inhibition of DNA biosynthesis.4–9