Abstract
TP53 mutations are found in over 50% of tumor types, including myeloproliferative neoplasms (MPNs). MPNs are characterized by a chronic phase, which may progress to secondary acute myeloid leukemia (sAML). Here, we discuss the physiological functions of p53 in hematopoiesis and its deregulation in MPNs. Additionally, we explore the mechanisms underlying TP53 mutations in the leukemic transformation of MPNs, including clonal evolution to multihit status and the role of inflammation and therapy. Finally, recent findings on the clinical impact of multihit TP53 mutations and potential strategies for targeting the p53 pathway in MPNs and sAML are presented.