Histopathology of Jak2V617F and Jak2wt BM transplant models. Histology of Jak2V617F- and Jak2wt-transduced Balb/c mice showing images of PB (A-B) and pathology in representative sections of BM (C-D), spleen (E-H), and liver (I-L). PB smear (B, 600 ×; Wright-Giemsa stain) of a representative Jak2wt animal displays normal white blood cell counts with an unremarkable differential. In contrast, PB smear (A, 600 ×; Wright-Giemsa stain) of a representative Jak2V617F mutant animal reveals marked leukocytosis consisting predominantly of maturing myeloid elements. Bone marrow images from Jak2wt animals display preserved marrow architecture with normal ratios of myeloid/erythroid elements and unremarkable megakaryocytes (D, 600 ×, H&E stain). In comparison, BM sections from Jak2V617F mutant animals demonstrate marrow elements composed of a prominent population of maturing myeloid cells with mildly to moderately increased numbers of megakaryocytes, including large, atypical forms occurring in occasional clusters (C; 600 ×, H&E stain) and showing emperipolesis of neutrophils in megakaryocyte cytoplasm. Spleen sections from Jak2V617F mice display complete effacement of normal splenic architecture (E; 40 ×, H&E stain) with a marked expansion of red pulp predominantly composed of maturing myeloid elements, frequent atypical megakaryocytes in clusters, and occasional erythroid elements (G; 600 ×, H&E stain) compared with unremarkable Jak2wt spleens (F, H; 40 ×, 600 ×, H&E stain). Liver images from Jak2V617F mice illustrate evidence of extensive extramedullary hematopoiesis in a perivascular and sinusoidal distribution (I; 100 ×, H&E stain) composed of frequent large, atypical megakaryocytes, maturing myeloid cells, and erythroid forms (K; 600 ×, H&E stain) notably absent in livers from Jak2wt animals (J, L; 100 ×, 600 ×, H&E stain).