Mechanism of action of TP53 and agents under investigation for TP53-mutated AML. (A) Mechanism of action of TP53: cellular stress and DNA damage activate the TP53 protein, which leads to downstream cell cycle arrest, DNA repair, and apoptosis. Cells containing mutations affecting the TP53 protein are not able to respond to stress and DNA damage appropriately, which increases the risk of neoplastic transformation. (B) Mechanism of action of magrolimab: the binding of CD47 on tumor cells to SIRPα on macrophages inhibits phagocytosis of tumor cells. Magrolimab is a monoclonal antibody that binds to CD47 and prevents it from binding to SIRPα, which thereby facilitates tumor cell phagocytosis. (C) Mechanism of action of APR-246: APR-246 is converted to MQ under physiological conditions. MQ binds to mutated TP53 and facilitates thermodynamic stabilization of the protein, thereby shifting equilibrium to the active form of TP53. APR-246 also exhibits TP53-independent activity through glutathione depletion, which increases lipid peroxidases and other reactive oxygen species, thereby promoting cell death through ferroptosis (not depicted). Created with BioRender.com.