Mechanistically, synergistic Jak2 V617F and loss-of-function Trp53 mutations have been noted to drive fully penetrant, transplantable AML in a murine model, pointing to a likely mechanism of transformation seen in many post-MPN AML and AML-EMD patients, involving BMP2/SMAD pathway activation [14, 15]. Jak2 and Trp53 biallelic inactivation together lead to an expansion of aberrant megakaryocytic-erythroid progenitors (MEPs), consistent with bipotential lineage markers seen in the identified cases in this study. The gene discussed is TP53; the disease is myeloproliferative neoplasm.