Figure 2.
Effect of IFN-α on histological features of the BM and spleen in Jak2V617F and Jak2V617F;Tyk2−/− mice. (A) The representative histological change in the BM after 8 weeks of 600 ng of ropeg-IFN-α treatment. Top, HE staining (100×); middle, HE staining (400×); bottom, silver (Ag) staining (200×). A yellow arrowhead indicates a megakaryocyte. (B) Megakaryocyte numbers in the BM after treatment with ropeg-IFN-α, assessed across 5 high-power fields (HPFs) per slide. Jak2V617F mice (n = 5 per each treatment group); Jak2V617F;Tyk2−/− mice (n = 5 per each treatment group). Data are presented as mean ± SD. Statistical significance was determined by the Tukey test after 1-way ANOVA. ∗∗P < .01. (C) Semiquantitative BM fibrosis grading (grades 0-3) after treatment with ropeg-IFN-α (n = 5 for each treatment group per each genotype). Statistical significance was determined by the Mann-Whitney U test for 2 groups; ∗P < .05. (D) Spleen weight after 8 weeks of treatment with ropeg-IFN-α. WT mice (n = 6 per PBS and n = 7 per ropeg-IFN-α treatment); Tyk2−/− mice (n = 6 per PBS and n = 6 per ropeg-IFN-α treatment); Jak2V617F mice (n = 9 per PBS and n = 7 per ropeg-IFN-α treatment); Jak2V617F;Tyk2−/− mice (n = 11 per PBS and n = 12 per ropeg-IFN-α treatment). Data are presented as mean ± SD. Statistical significance was determined by the Tukey test after 1-way ANOVA; ∗∗P < .01. (E) Histological changes in the spleen after treatment with ropeg-IFN-α. Top, HE staining (100×); middle, HE staining (400×); bottom, Ag staining (200×). A yellow arrowhead indicates a megakaryocyte. In Jak2V617F mice treated with PBS, myeloid lineage cells, including megakaryocytes, had invaded and destroyed normal splenic architecture, and fibrosis was evident. A ropeg-IFN-α treatment resolved fibrosis and restored the normal splenic architecture in these mice. Conversely, in Jak2V617F;Tyk2−/− mice, despite ropeg-IFN-α treatment, myeloid lineage cell invasion and fibrosis did not improve. (F) Megakaryocyte numbers in the spleen, assessed across 5 HPFs per slide. Jak2V617F mice (n = 5 per each treatment group); Jak2V617F;Tyk2−/− mice (n = 5 per each treatment group). Data are presented as mean ± SD. Statistical significance was determined by the Tukey test after 1-way ANOVA; ∗∗P < .01. HE, hematoxylin and eosin; n.s., not significant.

Effect of IFN-α on histological features of the BM and spleen in Jak2V617F and Jak2V617F;Tyk2−/− mice. (A) The representative histological change in the BM after 8 weeks of 600 ng of ropeg-IFN-α treatment. Top, HE staining (100×); middle, HE staining (400×); bottom, silver (Ag) staining (200×). A yellow arrowhead indicates a megakaryocyte. (B) Megakaryocyte numbers in the BM after treatment with ropeg-IFN-α, assessed across 5 high-power fields (HPFs) per slide. Jak2V617F mice (n = 5 per each treatment group); Jak2V617F;Tyk2−/− mice (n = 5 per each treatment group). Data are presented as mean ± SD. Statistical significance was determined by the Tukey test after 1-way ANOVA. ∗∗P < .01. (C) Semiquantitative BM fibrosis grading (grades 0-3) after treatment with ropeg-IFN-α (n = 5 for each treatment group per each genotype). Statistical significance was determined by the Mann-Whitney U test for 2 groups; ∗P < .05. (D) Spleen weight after 8 weeks of treatment with ropeg-IFN-α. WT mice (n = 6 per PBS and n = 7 per ropeg-IFN-α treatment); Tyk2−/− mice (n = 6 per PBS and n = 6 per ropeg-IFN-α treatment); Jak2V617F mice (n = 9 per PBS and n = 7 per ropeg-IFN-α treatment); Jak2V617F;Tyk2−/− mice (n = 11 per PBS and n = 12 per ropeg-IFN-α treatment). Data are presented as mean ± SD. Statistical significance was determined by the Tukey test after 1-way ANOVA; ∗∗P < .01. (E) Histological changes in the spleen after treatment with ropeg-IFN-α. Top, HE staining (100×); middle, HE staining (400×); bottom, Ag staining (200×). A yellow arrowhead indicates a megakaryocyte. In Jak2V617F mice treated with PBS, myeloid lineage cells, including megakaryocytes, had invaded and destroyed normal splenic architecture, and fibrosis was evident. A ropeg-IFN-α treatment resolved fibrosis and restored the normal splenic architecture in these mice. Conversely, in Jak2V617F;Tyk2−/− mice, despite ropeg-IFN-α treatment, myeloid lineage cell invasion and fibrosis did not improve. (F) Megakaryocyte numbers in the spleen, assessed across 5 HPFs per slide. Jak2V617F mice (n = 5 per each treatment group); Jak2V617F;Tyk2−/− mice (n = 5 per each treatment group). Data are presented as mean ± SD. Statistical significance was determined by the Tukey test after 1-way ANOVA; ∗∗P < .01. HE, hematoxylin and eosin; n.s., not significant.

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