TP53 encodes p53, a multifunctional transcription factor that serves as the central guardian of genome integrity by inducing cell cycle arrest, DNA repair, or apoptosis in response to cellular stress. Upon binding to specific DNA sequences, p53 regulates expression of approximately 500 target genes, including cyclin-dependent kinase inhibitors that halt cell division and pro-apoptotic factors like BAX while repressing anti-apoptotic proteins like Bcl-2. The protein's tumor suppressive activity depends on interactions with regulatory proteins, being activated by PPP1R13B/ASPP1 or TP53BP2/ASPP2 and inhibited by PPP1R13L/iASPP. TP53 mutations occur in approximately 50% of human cancers, making it the most frequently mutated gene in malignancy 1. These mutations produce diverse phenotypes with over four orders of magnitude difference in cancer-promoting efficiency across tissue types 2. In myeloid neoplasms, TP53 mutations are found in 10-15% of cases and represent one of the most important prognostic factors, with multihit TP53 mutations conferring particularly poor outcomes 3. The clinical significance extends beyond loss of tumor suppression, as TP53 mutations often confer resistance to chemotherapy and radiation therapy 4. Multiple therapeutic approaches are being pursued, including MDM2 inhibitors such as idasanutlin and navtemadlin, which aim to restore p53 function by blocking its negative regulator 1.