Loss of IL-1β from JAK2-mutant hematopoietic cells reduces MPN disease initiation. (A) Schematic drawing of the experimental setup for competitive transplantation at 1:100 dilution. BM from VF;GFP or VF;IL-1β−/−;GFP donor mice was mixed with a 100-fold excess of BM competitor cells from an IL-1β−/− donor. (B) Time course of blood counts from individual mice that received BM from VF;GFP (upper panel) or VF;IL-1β−/−;GFP donors (lower panel). (C) IL-1β protein levels in plasma and BM lavage (1 femur and 1 tibia) of mice with or without MPN phenotype is shown (right panel). Nonparametric Mann-Whitney 2-tailed t test was performed for statistical comparisons. (D) Time courses of GFP chimerism in the peripheral blood are shown. Multiple t tests were performed for statistical analyses. (E) Bar graphs show the percentages of mice that showed engraftment defined as GFP chimerism of >1% at 18 weeks after transplantation and the percentages of mice that developed MPN phenotype (elevated hemoglobin and/or platelet counts). P values in lower panel were computed using Fisher exact test. (F) Time course of mean blood counts and GFP chimerism in the peripheral blood of WT mice transplanted with BM from VF;GFP or VF;IL-1β−/−;GFP and IL-1β−/− competitor cells that developed MPN phenotype during 36-weeks follow-up. Multiple t tests were performed for statistical analyses. (G) GFP chimerism in HSPCs at 36 weeks after transplantation in the BM (left) and spleen (right) of WT mice transplanted with BM from VF;GFP or VF;IL-1β−/−;GFP and IL-1β−/− competitor cells that developed MPN phenotype. Multiple t tests were performed for statistical analyses. (H) Representative images of reticulin fibrosis staining in the BM (left panel) and hematoxylin and eosin staining in the spleen (right panel) of mice showed MPN phenotype at 36 weeks after transplantation. Histological grade of reticulin fibrosis in BM is shown in a bar graph (right). (I) Levels of inflammatory cytokines in BM lavage (1 femur and 1 tibia) and plasma of mice that displayed MPN phenotype at 36 weeks after transplantation. (J) Levels of IL-1 cytokines in the BM. Gray shaded area represents normal range. All data are presented as mean ± standard error of the mean (SEM); ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; and ∗∗∗∗P < .0001. See also supplemental Figures 1 and 2.

Loss of IL-1β from JAK2-mutant hematopoietic cells reduces MPN disease initiation. (A) Schematic drawing of the experimental setup for competitive transplantation at 1:100 dilution. BM from VF;GFP or VF;IL-1β−/−;GFP donor mice was mixed with a 100-fold excess of BM competitor cells from an IL-1β−/− donor. (B) Time course of blood counts from individual mice that received BM from VF;GFP (upper panel) or VF;IL-1β−/−;GFP donors (lower panel). (C) IL-1β protein levels in plasma and BM lavage (1 femur and 1 tibia) of mice with or without MPN phenotype is shown (right panel). Nonparametric Mann-Whitney 2-tailed t test was performed for statistical comparisons. (D) Time courses of GFP chimerism in the peripheral blood are shown. Multiple t tests were performed for statistical analyses. (E) Bar graphs show the percentages of mice that showed engraftment defined as GFP chimerism of >1% at 18 weeks after transplantation and the percentages of mice that developed MPN phenotype (elevated hemoglobin and/or platelet counts). P values in lower panel were computed using Fisher exact test. (F) Time course of mean blood counts and GFP chimerism in the peripheral blood of WT mice transplanted with BM from VF;GFP or VF;IL-1β−/−;GFP and IL-1β−/− competitor cells that developed MPN phenotype during 36-weeks follow-up. Multiple t tests were performed for statistical analyses. (G) GFP chimerism in HSPCs at 36 weeks after transplantation in the BM (left) and spleen (right) of WT mice transplanted with BM from VF;GFP or VF;IL-1β−/−;GFP and IL-1β−/− competitor cells that developed MPN phenotype. Multiple t tests were performed for statistical analyses. (H) Representative images of reticulin fibrosis staining in the BM (left panel) and hematoxylin and eosin staining in the spleen (right panel) of mice showed MPN phenotype at 36 weeks after transplantation. Histological grade of reticulin fibrosis in BM is shown in a bar graph (right). (I) Levels of inflammatory cytokines in BM lavage (1 femur and 1 tibia) and plasma of mice that displayed MPN phenotype at 36 weeks after transplantation. (J) Levels of IL-1 cytokines in the BM. Gray shaded area represents normal range. All data are presented as mean ± standard error of the mean (SEM); ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; and ∗∗∗∗P < .0001. See also supplemental Figures 1 and 2.

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