Figure 1.
Overexpression of Hmga2 accelerates the development of MF in Jak2V617Fknockin mice. (A) Hematocrit (HCT), (B) hemoglobin (Hb), (C) neutrophil (NE), and (D) platelet (PLT) counts in the peripheral blood were assessed at 12 and 24 weeks after bone marrow transplant (BMT) in WT-vector (n = 8), WT-Hmga2 (n = 9), Jak2VF/+-vector (n = 8), and Jak2VF/+-Hmga2 (n = 11) mice. (E) Spleen size and weight were significantly increased in Jak2VF/+-Hmga2 mice compared with Jak2VF/+-vector mice, whereas spleen size of WT-Hmga2 was modestly increased compared with WT-vector mice (n = 7-10). (F) BM cellularity was significantly increased in WT-Hmga2 mice compared with WT-vector mice, whereas Jak2VF/+-Hmga2 mice showed significantly decreased BM cellularity compared with Jak2VF/+-vector mice (n = 7-10). Student t test was used to compare 2 groups of mice. (G) Histopathologic analysis. Hematoxylin and eosin (H&E) staining of the BM and spleen sections (original magnification ×500) from WT-Hmga2 mice show normal morphology similar to that of WT-vector controls. BM sections from Jak2VF/+-vector mice show trilineage (megakaryocyte/erythrocyte/granulocyte) hyperplasia, whereas BM sections from Jak2VF/+-Hmga2 mice display fibrotic-appearing marrow with increased myelopoiesis. Spleen sections from Jak2VF/+-vector mice show trilineage extramedullary hematopoiesis, whereas spleens from Jak2VF/+-Hmga2 mice show increased myelopoiesis, increased and atypical megakaryocytes, and architectural distortion. Reticulin staining showed extensive fibrosis (grade 2 to 3) in the BM and spleens of Jak2VF/+-Hmga2 mice at 32 weeks after transplantation. BM and spleens of Jak2VF/+-vector mice exhibited little fibrosis at this stage. BM and spleens of WT-vector and WT-Hmga2 mice did not exhibit fibrosis. *P < .05; **P < .005.

Overexpression of Hmga2 accelerates the development of MF in Jak2V617Fknockin mice. (A) Hematocrit (HCT), (B) hemoglobin (Hb), (C) neutrophil (NE), and (D) platelet (PLT) counts in the peripheral blood were assessed at 12 and 24 weeks after bone marrow transplant (BMT) in WT-vector (n = 8), WT-Hmga2 (n = 9), Jak2VF/+-vector (n = 8), and Jak2VF/+-Hmga2 (n = 11) mice. (E) Spleen size and weight were significantly increased in Jak2VF/+-Hmga2 mice compared with Jak2VF/+-vector mice, whereas spleen size of WT-Hmga2 was modestly increased compared with WT-vector mice (n = 7-10). (F) BM cellularity was significantly increased in WT-Hmga2 mice compared with WT-vector mice, whereas Jak2VF/+-Hmga2 mice showed significantly decreased BM cellularity compared with Jak2VF/+-vector mice (n = 7-10). Student t test was used to compare 2 groups of mice. (G) Histopathologic analysis. Hematoxylin and eosin (H&E) staining of the BM and spleen sections (original magnification ×500) from WT-Hmga2 mice show normal morphology similar to that of WT-vector controls. BM sections from Jak2VF/+-vector mice show trilineage (megakaryocyte/erythrocyte/granulocyte) hyperplasia, whereas BM sections from Jak2VF/+-Hmga2 mice display fibrotic-appearing marrow with increased myelopoiesis. Spleen sections from Jak2VF/+-vector mice show trilineage extramedullary hematopoiesis, whereas spleens from Jak2VF/+-Hmga2 mice show increased myelopoiesis, increased and atypical megakaryocytes, and architectural distortion. Reticulin staining showed extensive fibrosis (grade 2 to 3) in the BM and spleens of Jak2VF/+-Hmga2 mice at 32 weeks after transplantation. BM and spleens of Jak2VF/+-vector mice exhibited little fibrosis at this stage. BM and spleens of WT-vector and WT-Hmga2 mice did not exhibit fibrosis. *P < .05; **P < .005.

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