Sequential Transformation of Polycythemia Vera to Myelofibrosis and KMT2A-Rearranged Acute Myeloid Leukemia Treated With Revumenib: A Rare Case of Clonal Evolution

Transformation of polycythemia vera (PV) into post-polycythemic myelofibrosis (MF) and subsequently acute myeloid leukemia (AML) represents one of the most aggressive trajectories among myeloproliferative neoplasms (MPNs). Post-MPN AML carries a median survival of approximately six months, particularly among older adults with adverse cytogenetics. We report the case of a 73-year-old man with JAK2-positive PV diagnosed in 2020 who progressed to MF in 2024 and developed AML later that year. Cytogenetic analysis revealed a KMT2A (11q23) rearrangement with KMT2A::ELL fusion, a finding rarely described in secondary AML arising from MPNs. Due to advanced age, transfusion dependence, and significant cardiovascular comorbidities, the patient was not a candidate for intensive chemotherapy or hematopoietic stem cell transplantation. He was initially treated with azacitidine and venetoclax but demonstrated disease progression. In the setting of a KMT2A::ELL fusion, therapy was transitioned to the menin inhibitor revumenib, resulting in short-term clinical stability and tolerability under continued supportive care.