Figure 2.
Figure 2. CALRdel/+ mice develop a myeloproliferative disease. (A) Time course of blood parameters of CALRdel/+ and control mice showing significantly increased platelets (Plt) and normal hematocrit and hemoglobin. A mildly elevated white blood cell (WBC) count is shown and is seen only in some cohorts. The CALRdel/+ mice were CALRfl/+ Mx1Cre+, and the littermate control mice CALR+/+ were CALRfl/+ Mx1Cre– or CALR+/+ Mx1Cre+. (B) Histologic analysis showing megakaryocytic hyperplasia with increased clustering and hyperlobated nuclei without fibrosis. (Left panel) Hematoxylin and eosin (H&E) staining performed on BM from mice at 3 to 4 months after poly I:C injection. (Middle panel) BM staining for reticulin (retic) showing no fibrosis. (Right panel) H&E staining of spleen showing normal splenic architecture. (C) CALRdel/+ mice show increased megakaryocyte colonies. Bar graphs showing significantly increased number of colony-forming unit–megakaryocyte (CFU-MK) colonies in BM. CFU-MK assay was performed in media with or without THPO. (D) CALRdel/+ mice show increased megakaryocytes. Flow cytometry was performed to assess the frequency (Freq) of BM megakaryocytes (MKs) (CD41+CD42+ or CD41+CD61+). (E) CALRdel/+ mice show reduced erythroblasts in BM. Flow cytometry was performed to assess the frequency of erythroblasts (CD71+Ter119+). Means ± standard error of the means (SEMs) are shown. *P < .05; **P < .01; ***P < .001. MNC, mononuclear cell; RBC, red blood cell.

CALRdel/+mice develop a myeloproliferative disease. (A) Time course of blood parameters of CALRdel/+ and control mice showing significantly increased platelets (Plt) and normal hematocrit and hemoglobin. A mildly elevated white blood cell (WBC) count is shown and is seen only in some cohorts. The CALRdel/+ mice were CALRfl/+ Mx1Cre+, and the littermate control mice CALR+/+ were CALRfl/+ Mx1Cre or CALR+/+ Mx1Cre+. (B) Histologic analysis showing megakaryocytic hyperplasia with increased clustering and hyperlobated nuclei without fibrosis. (Left panel) Hematoxylin and eosin (H&E) staining performed on BM from mice at 3 to 4 months after poly I:C injection. (Middle panel) BM staining for reticulin (retic) showing no fibrosis. (Right panel) H&E staining of spleen showing normal splenic architecture. (C) CALRdel/+ mice show increased megakaryocyte colonies. Bar graphs showing significantly increased number of colony-forming unit–megakaryocyte (CFU-MK) colonies in BM. CFU-MK assay was performed in media with or without THPO. (D) CALRdel/+ mice show increased megakaryocytes. Flow cytometry was performed to assess the frequency (Freq) of BM megakaryocytes (MKs) (CD41+CD42+ or CD41+CD61+). (E) CALRdel/+ mice show reduced erythroblasts in BM. Flow cytometry was performed to assess the frequency of erythroblasts (CD71+Ter119+). Means ± standard error of the means (SEMs) are shown. *P < .05; **P < .01; ***P < .001. MNC, mononuclear cell; RBC, red blood cell.

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