Transplantation of mutant NFE2 BM accelerates leukemic transformation – isolated myelosarcoma with mutated NFE2 in a PV patient. (A) Kaplan-Meier survival analysis of mice expressing various NFE2 mutations, wt-NFE2, or an empty control vector, as indicated. (Left) Primary recipients. (Right) secondary recipients transplanted with BM from primary recipients before the outbreak of acute leukemia. **P < .01 each of the mutations vs wt. (B) Hematological parameters of selected mice that developed leukemia. HCT, hematocrit; PLT, platelets; WBC, white blood cells. Blood counts indicating leukocytosis, anemia, and thrombocytopenia, the clinical hallmarks of leukemia, are highlighted in the black boxes. (C) FACS analysis of PB leukocytes of mice #882, #883, and #50. Cells were stained with CD11b and Ly6G/C to determine myeloid cells. (D) Histological analysis, CAE or hematoxylin and eosin–stained sections of the following organs of leukemic mice. #882, femur (1000×). #883, lung (10× and 1000×). #50: top, from left to right: spleen (25×, 400×, and 1000×); bottom, from left to right: femur (200× and 1000×), lung (10×). Bars: 200 μm (10×), 500 μm (25×), 50 μm (400×), 20 μm (1000×). (E) Diagnoses according to the Bethesda Classification of Nonlymphoid Hematological Malignancies¹⁰  in n = 26 knock-in mice expressing the Δ297-300aa mutation.⁹  (F) Histological analysis of the myelosarcoma diagnosed 15 months after initial PV diagnosis, found to carry the JAK2^V617F mutation as well as a NFE2 R273W, but no additional AML driver mutation. (Left) hematoxylin and eosin staining (right) anti-CD43 staining. Left and right: magnification 200×; size bar indicates 50 μm.