Targeting MDM2-induced p53 upregulation to enhance anti-leukemia immunity post allogeneic stem cell transplantation

Relapse after allo-HCT is a major cause of death of AML patients and results from immune evasion of AML blasts. Dysfunction of the p53 signaling pathway is frequent in AML and often caused by upregulation of the central p53 negative regulator Murine Double Minute 2 (MDM2). Besides its oncogenic effects p53 also regulates immune function and immune surveillance of solid cancer. We hypothesize that p53 also controls immune-related genes in AML cells and that p53 reactivation via MDM2-inhibition may enhance the immunogenicity of AML cells to allogeneic T cells. In total 18 samples were analyzed, including 6 replicates from DMSO control, 6 replicates from MDM2 inhibitor RG7112 and 6 replictes from MDM2 inhibitor HDM201.