Abstract
Methotrexate (MTX) and 6-mercaptopurine (6-MP) are widely used in the maintenance treatment of acute lymphoblastic leukemia (ALL) in children. Based on their biochemical interactions there are reasons to support a combination therapy of both drugs. MTX binds tightly to dihydrofolate reductase, the enzyme that catalyses the reduction of dihydrofolate to tetrahydrofolate. Tetrahydrofolate coenzymes are required for one-carbon transfer reactions in purine de novo synthesis and thymidylate biosynthesis (Figure 1). As a consequence a purine-less and a thymidylate-less state will occur, ultimately resulting in inhibition of DNA biosynthesis [1–10].
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© 1987 Martinus Nijhoff Publishers, Dordrecht
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De Abreu, R.A., Bökkerink, J.P.M., Bakker, M.A.H., Hulscher, T.W., Van Baal, J.M. (1987). The effect of methotrexate on purine and pyrimidine deoxyribonucleoside triphosphate pools and on cell viability and cell-phase distribution in malignant human T- and B-lymphoblasts. In: Poplack, D.G., Massimo, L., Cornaglia-Ferraris, P. (eds) The Role of Pharmacology in Pediatric Oncology. Developments in Oncology, vol 44. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-4267-7_14
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DOI: https://doi.org/10.1007/978-94-009-4267-7_14
Publisher Name: Springer, Dordrecht
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