Asparaginase (ASNase) is a key component in the treatment of ALL; it acts by depleting asparagine (Asn) from the blood. A poor response to ASNase is associated with increased relapse risk. Lymphocytes and leukemic blasts are selectively dependent on the exogenous supply of Asn, and exposure to ASNase leads to a cessation of growth and the induction of cell death. Cellular quiescence or apoptosis induction in leukemic cells in response to ASNase is dependent on the genetic makeup of the leukemia and the extent of Asn depletion in the cellular microenvironment. The goal of this project is to obtain detailed molecular insights into how kinase signaling affects the cellular response to ASNase-induced nutrient starvation, and to identify and validate kinase inhibitors that synergize with ASNase to increase treatment efficacy and reduce the number of relapses.