Transplantation of bone marrow cells expressing CSF3R and SETBP1 mutations results in rapidly lethal leukemia. (A) Survival curves for SETBP1 primary transplantation model. Transplantation of 25 000 lineage-negative CSF3R^T618I plus SETBP1^D868N cells, with 190 000 nontransfected carrier bone marrow cells, into lethally irradiated recipient mice resulted in rapidly lethal aggressive leukemia (n = 5-7). The median survival of SETBP1^D868N mice was 25.9 weeks. (B) Peripheral blood white blood cell (WBC) differentials at posttransplantation day 17. (C) Peripheral WBC differentials at day 21. (D) Peripheral WBC counts over time. (E) Representative hematoxylin and eosin (H&E)–stained tibia cross-sections showing increased cellularity at time of death with SETBP1^D868N alone and CSF3R^T618I plus SETBP1^D868N. (F) Terminal spleen weight. (G) Representative images of H&E-stained spleens showing splenic architecture changes. (H) Terminal WBC count. (I) Terminal liver weight. (J) Terminal body weight. Statistics: 1-way analysis of variance with Dunnett correction. *P < .05, **P < .01.