P53, a critical transcription factor that inhibits cell division or survival in response to various stresses such as DNA damage, and acts as a key fail-safe mechanism of cellular anti-cancer defenses, is central to hematopoietic stem cell functions and its aberrations affect AML evolution, biology, and therapy response [40], whereas MDM2 is the major E3 ubiquitin ligase for P53 degradation. The gene discussed is TP53; the disease is cancer.