Rapidly proliferating tumors attempt to meet the demands for nucleotide biosynthesis by up regulating folate pathways that provide the building blocks for pyrimidine and purine biosynthesis. In particular, the key role of mitochondrial folate enzymes in providing formate for de novo purine synthesis and for providing the one carbon moiety for thymidylate synthesis has been recognized in recent studies. We have shown a significant correlation between the up regulation of the mitochondrial folate enzymes, high proliferation rates and sensitivity to the folate antagonist, methotrexate (MTX). Burkitt's lymphoma and Diffuse Large cell lymphoma tumor specimens have the highest levels of mitochondrial folate enzyme expression and are known to be sensitive to treatment with MTX.

 

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