Histopathologic characterization of the MPN induced by Jak2V617F. (A) Peripheral blood smears show increased RBCs, leukocytes, and platelets in induced heterozygous and homozygous Jak2V617F mice (12 weeks after induction). Leukocytosis and thrombocytosis were more pronounced in homozygous Jak2V617F mice compared with heterozygous Jak2V617F animals. Arrows point to reticulocytes. (B) BM sections from induced Jak2V617F heterozygous and homozygous mice show trilineage hyperplasia (hematoxylin and eosin staining, ×500). (C) Reticulin staining on the BM sections (×500) shows mild fibrosis (grade 1) in older Jak2V617F heterozygous mice (24 weeks after induction), whereas homozygous mice show more reticulin fibrosis (grade 2) than heterozygous mice. (D) Spleens from heterozygous and homozygous Jak2V617F mice display extensive destruction of normal splenic architecture (×40 and ×500) with attenuated white pulp and markedly expanded red pulp, increased numbers of megakaryocytes, and clusters of immature erythroid precursors. (E) Reticulin staining of the heterozygous spleen shows increased fibrosis of the white pulp and slight reticulin fibrosis of the red pulp. Spleens from homozygous mice show pronounced reticulin fibrosis in the white pulp and also increased fibrosis in the red pulp compared with heterozygous mice.