Homozygous JAK2V617F expression is associated with increased megakaryopoiesis but reduced platelet survival. (A) Platelets from JAK2^R/R mice have reduced survival compared with WT and JAK2^R/+ mice as measured by labeling platelets on day 0 and monitoring the labeled cells remaining over a 7-day time course. (B) Splenectomized JAK2^R/R mice also show reduced platelet survival. Asterisks indicate significant differences between JAK2^R/R and JAK2^R/+ mice at each time point using Student t test (*P < .05; **P < .01; ***P < .001). Data are shown as mean ± SEM. (C) Western blot analysis shows reduced Bcl-xL but not Bax in homozygous platelets. Homozygous platelets show reduced level of P-selectin (D) and fibrinogen binding (E) in response to CRP. The histogram represent % of maximum response in WT controls. (F) JAK2^R/R mice have increased numbers of megakaryocytes in BM and spleen compared with JAK2^R/+ and WT mice. Megakaryocytes were visualized by histology and counted throughout 10 high-power fields (hpf, ×40 objective) per section. (G) Megakaryocyte colony-forming unit assays showed an increase in megakaryocyte progenitors from 8-week-old JAK2^R/R mice in BM (left panel) and spleen (right panel) with and without thrombopoietin (TPO). Asterisks indicate significant differences by Student t test (*P < .05; **P < .01). Data are shown as mean ± SEM.