Figure 4
Figure 4. Mice transplanted with Jak2V617F mutant LT-HSCs develop MPN and myelofibrosis. (A) Histopathologic (HE) sections of BM from a representative mouse transplanted with Jak2+/VF ST-HSC + MPP cells (n = 4 in group) or Jak2+/VF LT-HSC cells (n = 3 in group), demonstrating diffuse erythroid hyperplasia and megakaryocyte hyperplasia in the Jak2+/VF LT-HSC recipient. The Jak2+/VF LT-HSC recipient also shows evidence of megakaryocytic clustering, enlarged forms with bizarre, hypernucleated nuclei, marked emperipolesis, and abnormal megakaryocyte localization in marrow sinuses or in association with trabecular bone. These abnormalities are not seen in the Jak2+/VF ST-HSC + MPP recipient. (B) Reticulin sections of BM from a representative mouse transplanted with Jak2+/VF ST-HSC + MPP cells (n = 4 in group) or Jak2+/VF LT-HSC cells (n = 3 in group), demonstrating a fine reticulin fiber network with crossing fibers deposition consistent with grade 1-2 reticulin fibrosis in the Jak2+/VF LT-HSC recipient. These abnormalities are not seen in the Jak2+/VF ST-HSC + MPP recipient. (C) Histopathologic (HE) sections of spleen from a representative mouse transplanted with Jak2+/VF ST-HSC + MPP cells (n = 4 in group) or Jak2+/VF LT-HSC cells (n = 3 in group), demonstrating erythroid hyperplasia and megakaryocyte hyperplasia with clustering and atypical nuclear features in the Jak2+/VF LT-HSC recipient. These abnormalities are not seen in the Jak2+/VF ST-HSC + MPP recipient.

Mice transplanted with Jak2V617F mutant LT-HSCs develop MPN and myelofibrosis. (A) Histopathologic (HE) sections of BM from a representative mouse transplanted with Jak2+/VF ST-HSC + MPP cells (n = 4 in group) or Jak2+/VF LT-HSC cells (n = 3 in group), demonstrating diffuse erythroid hyperplasia and megakaryocyte hyperplasia in the Jak2+/VF LT-HSC recipient. The Jak2+/VF LT-HSC recipient also shows evidence of megakaryocytic clustering, enlarged forms with bizarre, hypernucleated nuclei, marked emperipolesis, and abnormal megakaryocyte localization in marrow sinuses or in association with trabecular bone. These abnormalities are not seen in the Jak2+/VF ST-HSC + MPP recipient. (B) Reticulin sections of BM from a representative mouse transplanted with Jak2+/VF ST-HSC + MPP cells (n = 4 in group) or Jak2+/VF LT-HSC cells (n = 3 in group), demonstrating a fine reticulin fiber network with crossing fibers deposition consistent with grade 1-2 reticulin fibrosis in the Jak2+/VF LT-HSC recipient. These abnormalities are not seen in the Jak2+/VF ST-HSC + MPP recipient. (C) Histopathologic (HE) sections of spleen from a representative mouse transplanted with Jak2+/VF ST-HSC + MPP cells (n = 4 in group) or Jak2+/VF LT-HSC cells (n = 3 in group), demonstrating erythroid hyperplasia and megakaryocyte hyperplasia with clustering and atypical nuclear features in the Jak2+/VF LT-HSC recipient. These abnormalities are not seen in the Jak2+/VF ST-HSC + MPP recipient.

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