Clinical Study

Polymorphisms of MTHFR Associated with Higher Relapse/Death Ratio and Delayed Weekly MTX Administration in Pediatric Lymphoid Malignancies

Figure 1

Schematic representation of methotrexate action. MTX inhibits folic metabolism through two mechanisms: MTX inhibits DHFR, which leads to the depletion of THF compounds, resulting in impairment of purine and thymidine synthesis. Polyglutamated MTX inhibits TS directly, which causes depletion of DNA synthesis. MTX: methotrexate; DHFR: dihydrofolate reductase; DHF: dihydrofolate; THF: tetrahydrofolate; TS: thymidylate synthase; MTHFR: methylenetetrahydrofolate reductase; MTX : MTX glutamates; dTMP: deoxythymidine monophosphate; dUMP: deoxyuridine monophosphate.
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