Figure 5
Ruxolitinib ameliorates thrombocytosis in CALR mutation-induced ET. (A) Differential blood counts in WT mice treated with vehicle (WT-vehicle; n=11) for 4 weeks and in CALRdel52-TG mice treated with either vehicle (TG-vehicle; n=8) or 90 mg/kg bid ruxolitinib for 4 weeks (TG-Ruxo) (n=7). CALRdel52-TG demonstrate thrombocytosis, which is partially resolved by ruxolitinib therapy. Ruxolitinib also decreased white blood cell counts in TG mice. The paired data between pre- and post-treatment were analyzed with a paired two-tailed t-test. P-values are shown. (B) Upper panel: histological changes in CALRdel52-TG mice following ruxolitinib treatment for 4 weeks. BM were stained with hematoxylin and eosin (HE). TG mice treated with vehicle exhibit megakaryocyte proliferation in both BM and spleen (b, e and h). TG mice treated with ruxolitinib show a marked reduction of megakaryocytes in these organs (c, f and i). Lower left panel: the number of megakaryocytes is decreased by ruxolitinib therapy in TG mice. Lower center panel: the absolute numbers of nucleated cells in BM (one femur and one tibia) and spleen. Compared with vehicle-treated mice, TG treated with ruxolitinib show decreased nucleated cells in BM and spleen. Lower right panel: spleen weights are decreased by treatment with ruxolitinib but not vehicle. ††P<0.01 vs WT mice. *P<0.05 and **P<0.01 vs TG-vehicle mice. (C) The proportion of myeloid cells (Mac1/Gr1), T cells (CD3), B cells (B220), erythroid cells (CD71/Ter119 and Ter119) and megakaryocytes (CD41) in the BM and spleen. Ruxolitinib treatment in TG mice had little effect on the frequency of these cells, with the exception of B220 B cells and CD71/Ter119 erythroid cells. ††P<0.01 vs WT mice. *P<0.05 and **P<0.01 vs TG-vehicle mice. (D) The proportions of HSCs and progenitors in BM. TG treated with ruxolitinib show decreased HSC, MPP and LSK frequencies compared with TG mice treated with vehicle. ††P<0.01 vs WT mice. *P<0.05 and **P<0.01 vs TG-vehicle mice. All data are presented as means±s.e.m.
