Figure 5.

A schematic diagram of the anti-leukemic functional roles of FBP1 and FBP-activated P53 in AML blasts in vitro: There are multifaceted anti-leukemic functions of FBP1 in the treatment of AML blasts; FBP1 inhibits the process of glycolysis by reducing key intermediate metabolites such as pyruvate (BOX1) and regulates blast differentiation via changes in cellular signaling. FBP1-disturbed glycolysis can induce stress in the mitochondria (BOX2), leading to the reduction in COX2 in the OXPHOS process. To maintain metabolic homeostasis and survive, FBP1-MV4-11 blasts can activate the quality control system of mitochondria via upregulation of PINK1 (BOX3). The activated mitophagy and autophagy can replenish key metabolites such as fatty acids and glutamine, to either promote the regeneration of dysfunctional mitochondria (BOX3) or prevent cell death (BOX4). In addition to its glycolytic regulatory function, FBP1 can increase pro-apoptotic proteins and tumor suppressors—such as caspase-3, BAX, and P53—while decreasing hypoxic oncogenes such as HIF1A (not shown), leading to programmed leukemic cell death (BOX4).