Cux1^lowmice develop a fatal MDS/MPN that is reversed by CUX1 reexpression. Adult Cux1^low and littermate Ren mice were continuously treated with dox starting at 6 to 10 weeks of age. (A) Kaplan-Meier survival plot of Cux1^low (n = 20), Cux1^mid (n = 11), and Ren mice (n = 19) shows that Cux1^low mice have significantly decreased survival (log-rank test). (B) Complete blood cell counts of peripheral blood samples collected over time demonstrate a progressive anemia and WBC expansion. (C) Flow cytometric analysis of PB granulocytes (CD11b⁺/Gr1⁺), monocytes (CD11b⁺/Gr1⁻), B cells (B220⁺), and T cells (CD3⁺) over time. (D) Representative images of spleens collected at the time that Cux1^low mice were euthanized because of disease. (E) Spleens and (F) livers were weighed and normalized to body weight. (G) Total leukocyte counts from BM (femurs, tibias, and hipbones) and spleens were enumerated at the time of euthanization. (H) Absolute monocyte and granulocyte cell counts are shown from the BM and spleen at the time of euthanization. (I) Absolute lymphoid cell counts from the BM are provided. (J) HSPC populations were quantified at the time of euthanization. (J, left) LSK⁺ (Lin⁻/Sca1⁺/c-Kit⁺) cells and MP (Lin⁻/Sca1⁻/c-Kit⁺) are shown. (Center) LSK were further gated for LT-HSC (LSK⁺/CD34⁻/Flt3⁻), ST-HSC (LSK⁺/CD34⁺/Flt3⁻), and MPP (LSK⁺/CD34⁺/Flt3⁺). (Right) Within the MP population, cells were separated into CMP (CD34⁺/CD16/32^low), GMP (Lin⁻/c-Kit⁺/Sca1⁻/CD34⁺/CD16/32^high), and MEP (Lin⁻/c-Kit⁺/Sca1⁻/CD34⁻/CD16/32⁻). (K) After 7 months of continuous dox exposure, dox treatment was ceased for a cohort of mice, and hematopoietic populations were assessed over time. PB indices show a normalization of RBC and WBC counts. (L) Flow cytometry shows a normalization of PB granulocyte frequency. Additional data are provided in supplemental Figure 5. The mean ± SD is shown. Student t test *P ≤ .05, **P ≤ .01, ***P ≤ .001.