Histopathological analysis of VavCre;FF1 and MxCre;FF1 mice (20 weeks). H&E staining of bone marrow of both double transgenic mice (A) show trilineage hyperplasia with markedly increased numbers of megakaryocytes, most of which are morphologically abnormal (hyperchromatic, hyperlobulated nuclei, bizarre nuclear configuration) and present in clusters. (B) Dilated sinusoids were observed in 3/3 VavCre;FF1 mice in the bone marrow, but were absent in the 3 examined MxCre;FF1 mice. (C) Reticulin staining (Gömöri) demonstrates fibrosis in bone marrow. (D) Fibrosis also was seen in the spleen (only VavCre;FF1 is shown). (E) H&E staining of spleens demonstrate destruction of normal splenic architecture by atypical hematopoiesis in both MxCre;FF1 and VavCre;FF1 mice. In particular, megakaryocytes are markedly increased in numbers and display the same atypical morphology as in the bone marrow. (F) The liver shows extramedullary hematopoiesis indicated by the presence of megakaryocytes and clusters of granulopoiesis or erythropoiesis. (G) Megakaryocytes (arrowhead) were detected in the lung of MxCre;FF1 mice. VavCre;FF1 mice were not analyzed.