The paradigm of metabolic therapy in ALL is the use of Asparaginase, which takes advantage of the failure of ALL blasts to express Asparagine synthetase, making blasts dependent on exogenous sources of asparagine.24 Although methotrexate is another established approach to target leukemic cell metabolism (through dihydrofolate reductase inhibition), it is only recently that an alternative strategy, arginine depletion, has become viable.25 This evidence concerns the gene DHFR and acute lymphoblastic leukemia.