Deletion of Dusp1 is synthetically lethal to CSF3R-induced leukemia. (A) Experimental design for evaluating the role of Dusp1 in CNL/aCML. (B) Percent CFUs from the C57Bl/6-WT and Dusp1^-/- Kit⁺ cells expressing leukemic CSF3R^T618I (proximal) and CSF3R^{T618I/Q741∗}(compound mutation). The data shown are the mean colony number from 2 independent experiments ± SD. (C-E) Shown are the leukemia development in mice that received transplantation with wild-type BM-derived Kit⁺ cells expressing CSF3R^T618I and CSF3R^{T618I/Q741∗}. (C) PB smear (top panel) and white blood cell (WBC) levels determined biweekly (bottom panel). (D) Survival curve of leukemic mice that received transplantation with CSF3R^T618I and CSF3R^{T618I/Q741∗} expressing Kit⁺ cells. (E) Shown is the venus-positive cells as a surrogate leukemic burden from the PB. Dotted lines represent normal WBC levels. Representative data are from the 2 independent transplant experiments. (F-H) Mice that received transplantation with Dusp1-deficient BM-derived Kit+ cells expressing CSF3R^T618I and CSF3R^{T618I/Q741∗} are gradually eradicated from the BM. (F) PB smear (top) and WBC levels determined biweekly (bottom) do not show any elevation of WBC levels. (G) Survival curve showing prolong survival of mice that received transplantation with Dusp1-deficient Kit⁺ cells expressing CSF3R^T618I and CSF3R^{T618I/Q741∗}. (H) Kit cells expressing CSF3R^T618I and CSF3R^{T618I/Q741∗} are progressively removed from the PB while maintaining the vector-expressing cells. Representative data are from 2 independent experiments (5 mice per group), shown as the means ± SD. ∗P < .05; ∗∗P < .01; and ∗∗∗P < .001.