Glutamine depletion by asparaginase indirectly inhibits mTOR activity via decreased leucine uptake in AML. AML cells accumulate intracellular glutamine through the activity of the SLC1A5 transporter. Intracellular glutamine in turn promotes leucine uptake via the SLC7A5 amino acid translocator. Leucine then facilitates Rheb15-dependent mTOR activation at the lysosomal surface resulting in increased cap-dependent mRNA translation. Asparaginase can efficiently inhibit this pathway via deamination of glutamine.