CXCL4 knockdown reduces thrombocytosis and fibrosis grade in JAK2^(V617F) and MPL^W515L murine models of PMF. C57BL/6 recipient mice received lethal irradiation at 10 weeks of age followed by either WT or Cxcl4^−/− HSPCs transduced with JAK2^(V617F), MPL^W515L, or WT control retroviral vectors (n = 5 per group for JAK2^(V617F) experiment; n = 6 per group for MPL^W515L experiment). Mice were euthanized at 182 days after transplantation for the JAK2^(V617F) experiment and 21 days’ posttransplantation for the MPL^W515L experiment. (A) Platelet counts from peripheral blood. (B) Representative images of hematoxylin and eosin (H&E) staining in femurs. Original magnification ×20; scale bar, 100 μm. (C) Quantification of the mean area of MKs in control or JAK2^(V617F)-driven BM. (D) Representative images of reticulin staining in control or JAK2^(V617F)-driven BM. Original magnification ×20; scale bar, 100 μm. (E) Quantification of myelofibrosis grade based on reticulin staining in control or JAK2^(V617F)-mutated BM (Kruskal-Wallis multiple comparisons test). (F) Platelet and red blood cell (RBC) counts in peripheral blood. (G) Representative images of H&E staining in femurs. Original magnification ×20; scale bar, 100 μm.(H) Representative images of reticulin staining in femurs. Original magnification ×20; scale bar, 100 μm. (I) Quantification of myelofibrosis grade based on reticulin staining in control or MPL^W515L-mutated BM (Kruskal-Wallis multiple comparisons test). Data are shown as mean ± standard error of the mean, 1-way analysis of variance followed by Tukey’s post hoc test unless otherwise indicated. *P < .05, ***P < .001, ****P < .0001.