Phenotype of the SETBP1^G870S mouse. (A) Gross examination of SETBP1^LSL (first panel) and SETBP1^G870S (second and third panel) mice at autopsy, showing massive enlargement of the spleen and liver in SETBP1^G870S mice (red arrows). The fourth panel shows the spleen of SETBP1^LSL (left) and SETBP1^G870S mouse (right); the red arrow points to a splenic infarction occurring in SETBP1^G870S. (B-C) Spleen size (B) and weight (C) of SETBP1^LSL (green) and SETBP1^G870S (orange) mice, confirming massive spleen enlargement. Statistical analysis was performed using a 2-tailed t test. (D) Total WBC counts reported over the course of a 150-day follow-up for SETBP1^G870S (orange) and SETBP1^LSL (green) mice. (E) Hematoxylin and eosin (H&E) stained PB cytospins of a 60-day SETBP1^G870S mouse showing accumulation of mostly mature neutrophils with less abundant monocytes. (F) Violin plot showing the fraction of myeloid cells over the total WBC count in SETBP1^LSL (green) and SETBP1^G870S (orange) mice at 120 days, as determined by pathologist’s counts on cytospin slides. Statistical analysis was performed using a 2-tailed t test. (G) (Left) fluorescence-activated cell sorter (FACS) analysis of representative SETBP1^LSL (green) and SETBP1^G870S (orange) PB mononuclear cell (PBMCs); CD11b vs Ly6G (upper) and CD3 vs GFP (lower) plots are shown, displaying massive expansion of CD11b⁺ myeloid cells and dramatic reduction of CD3⁺ lymphocytes. Blood samples were collected at 120 days; (right) aggregated FACS data (n = 6). (H) Kaplan-Meier OS analysis. P values were calculated with the use of a log-rank test, and mice were stratified according to their genotype (SETBP1^G870S, heterozygous, orange; SETBP1^G870S, homozygous, red; SETBP1^LSL, green). Tick marks indicate censored data.