Anti–IL-1β antibody reduces MPN disease initiation in a mouse model of JAK2-V617F–driven clonal hematopoiesis. (A) Schematic drawing of the experimental setup for competitive transplantation at 1:100 dilution. BM cells from a VF;GFP donor mouse were mixed with a 100-fold excess of WT BM competitor cells and transplanted into lethally irradiated WT recipient mice. Transplanted mice were randomized into 2 treatment arms (n = 36 per group) and treated with anti–IL-1β antibody or isotype control for 18 weeks, starting 1 day after transplantation (Tx). (B) The percentage 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) are indicated. P value was computed using Fisher exact test. (C-D) The upper panel shows the time course of blood counts from all individual mice for the 2 treatment arms, as indicated. The lower panel shows the mean GFP chimerism in the peripheral blood for mice with MPN phenotype (MPN) and without MPN phenotype (no MPN) that engrafted, defined as GFP chimerism of >1% at 18 weeks. Erythrocytes (Ter119), platelets (CD61), and granulocytes (Gr1) cells are shown separately. Multiple t tests were performed for statistical analyses. (E) GFP chimerism in HSPCs after 18 weeks of treatment. Multiple t tests were performed for statistical analyses. All data are presented as mean ± SEM; ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; and ∗∗∗∗P < .0001. See also supplemental Figures 7 and 8.