CALR^del/delmice develop an extreme myeloproliferative disease with MF. (A) CALR^del/del mice develop marked thrombocytosis. Bar graphs showing significantly increased platelets, elevated WBC counts, and reduced hematocrit (Hct) in CALR^del/del mice at 3 to 4 months after poly I:C. The CALR^del/del mice were CALR^fl/fl Mx1Cre⁺, the CALR^del/+ mice were CALR^fl/+ Mx1Cre⁺, and the control mice (CALR^wt/+) were CALR^fl/+ Mx1Cre^– or CALR^+/+ Mx1Cre⁺. (B) CALR^del/del mice show splenomegaly. (C) CALR^del/del mice show striking megakaryocytic hyperplasia. Tissues from mice at 7 to 8 months after poly C:I were taken for histologic analysis. (Left panel) H&E staining of BM showing almost complete effacement of normal hematopoiesis by megakaryocytes and displaying nuclear atypia in CALR^del/del mice. (Middle panel) Silver staining for reticulin showing BM fibrosis in CALR^del/del mice. (Right panel) H&E staining of spleen showing destruction of splenic architecture in CALR^del/del mice. (D) CALR^del/del mice show markedly increased frequencies of HSCs. Flow cytometry was performed and HSCs were defined as Lin^–Sca1⁺cKit⁺CD150⁺CD48^–. (E) CALR^del/del mice show markedly increased frequencies of megakaryocytic progenitors (MkPs) (Lin^–Sca1⁻cKit⁺CD150⁺CD41⁺). (F) CALR^del/del mice show markedly increased frequencies of myeloid progenitors (Prog) in spleen. Flow cytometry was performed, and myeloid progenitors were defined as the Lin^–Sca1⁻cKit⁺ population. (G) CALR^del/del mice show significantly reduced numbers of erythroblasts. Flow cytometry was performed and erythroblasts were defined as CD71⁺Ter119⁺. Data are shown as mean ± SEM. *P < .05; **P < .01; ***P < .001.