Although AICART inhibition and the accumulation of AICAR and its metabolite AICA have been proposed to mediate anti-inflammatory effects [26], [27], [28], [34], [36], [37], [39], in vitro studies with leukemia cells and primary human T lymphocytes indicate that PPAT is the primary site of inhibition of purine biosynthesis by methotrexate [22], [55]. The gene discussed is PPAT; the disease is leukemia.