Polycythemia Vera Transforming to Pure Erythroid Leukemia: A Diagnostic Mimic of Thrombotic Microangiopathy With High-Risk TP53 Biology

Leukemic transformation of polycythemia vera (PV) to acute myeloid leukemia (AML) with a predominantly erythroid blast population is rare and carries a poor prognosis, particularly when driven by a TP53 mutation. We report a 55-year-old man with JAK2 V617F-positive PV, previously noted on surveillance biopsy to harbor a TP53 mutation and Grade 2 marrow fibrosis, who presented three years later with pancytopenia, schistocytosis, hyperferritinemia, hypofibrinogenemia, and altered mental status. The initial clinical presentation raised concern for thrombotic thrombocytopenic purpura (TTP), while the presence of rare circulating blasts and coagulopathy also prompted consideration of acute promyelocytic leukemia (APML). Empiric plasma exchange, corticosteroids, and all-trans retinoic acid were initiated. ADAMTS13 activity and PML-RARA FISH subsequently returned negative. The patient deteriorated with multiorgan failure and expired before leukemia-directed therapy could be initiated. Postmortem bone marrow results demonstrated greater than 90% erythroid blasts with TP53 protein overexpression, a TP53 p.C238Y mutation (VAF 66%), and a triploid karyotype with 7p and 19p abnormalities, consistent with pure erythroid leukemia (PEL) arising from an antecedent myeloproliferative neoplasm. This case highlights the diagnostic challenges posed by overlapping clinical features of TTP and APML, including limitations in immunophenotypic assignment of the erythroid lineage. Importantly, it provides a longitudinally documented example of a TP53 mutation detected three years before overt transformation and describes a previously unreported presentation mimicking both TTP and APML.