MPLW515L Is a Novel Somatic Activating Mutation in Myelofibrosis with Myeloid Metaplasia
Figure 4
MPLW515L and MPLWT Bone Marrow Transplant Model Histopathology
Histology of MPLW515L-transduced and MPLWT-transduced Balb/C mice showing images of peripheral blood (A and B) and histopathology in representative sections of bone marrow (C and D), spleen (E–H), and liver (I–L). Peripheral blood smear (B) (600×, Wright-Giemsa) of a representative MPLWT animal displays an unremarkable white blood cell and platelet count. In contrast, peripheral blood smear (A) (600×, Wright-Giemsa) of a representative MPLW515L mutant animal reveals marked thrombocytosis and leukocytosis comprising a predominant population of maturing myeloid cells as well as frequent nucleated erythroid forms. Bone marrow images from MPLWT animals display preserved marrow architecture with maturing trilineage hematopoiesis (D) (600×, hematoxylin and eosin [H&E]). Comparatively, bone marrow sections from MPLW515L mutant animals demonstrate marrow elements comprising a prominent population of maturing myeloid cells with increased numbers of megakaryocytes including atypical and dysplastic forms occurring in frequent clusters (C) (600×, H&E) and showing emperipolesis of neutrophils in megakaryocyte cytoplasm. Spleen sections from MPLW515L mice display complete effacement of normal splenic architecture (E) (40×, H&E) with a marked expansion of red pulp that is composed of an admixture of maturing myeloid and erythroid elements and numerous numbers of atypical megakaryocytes (G) (600×, H&E) compared with MPLWT spleens (F and H) (40× and 600×, H&E), which display a relative preservation of normal spleen architecture and the presence of only maturing erythroid forms in the red pulp. Liver images from MPLW515L mice illustrate evidence of extensive extramedullary hematopoiesis in a perivascular and sinusoidal distribution (I) (100×, H&E) composed predominantly of a population of maturing erythroid elements with frequent large atypical megakaryocytes and occasional admixed myeloid forms (K) (600×, H&E). In comparison, only small, focal areas of nucleated erythroid cells were observed in livers from MPLWT animals (J and L) (100× and 600×, H&E).