Fig. 3

Major mechanisms through which asparagine affects the development of leukaemia. ASNase, a chemotherapeutic drug that targets circulating asparagine, has been approved in the treatment of leukaemia. Asparagine deficiency reduces MYC expression and induces apoptosis in leukemic cells. Leukemic cells initiate a series of stress responses in this situation. Initiation of autophagy, increased expression of ASNS, and decomposition of proteins can increase intracellular asparagine levels. Moreover, asparagine from MSCs, intestinal absorption, and the pancreas increase these levels further. As a result, these compensatory responses decrease the sensitivity of leukemic cells to ASNase