Sustained CUX1 loss is required for the development of t-MNs. Restoration of CUX1 prevents t-MNs. (A) Mutational burden in primary samples from patients with CUX1-wild type (n = 1731) and CUX1 mutations or deep deletions (n = 35). Samples are from patients with myeloid neoplasms, including AML, MDS, MPN, and MDS/MPN. AACR GENIE Cohort v9.0⁸⁸  (B) Ren and Cux1^low mice were treated with Dox and ENU as in Figure 6. One month after ENU, Dox was removed and CUX1 expression restored in a cohort of Ren (n = 6) and Cux1^low (n = 7) mice (dashed lines). A cohort of Ren (n = 3) and Cux1^low (n = 3) mice continued to receive Dox (solid lines). Ren mice were euthanized when Cux1^low mice showed signs of disease. (C) RI-RIV erythroid precursor populations quantified as a percentage of erythroblasts in the spleen. The mean ± SD is shown, and P values were calculated using a 2-way ANOVA. (D) Representative images of spleens at autopsy from Ren and Cux1^low mice at autopsy. (E) Representative images from Ren and Cux1^low spleens stained with H&E are shown; original magnification, ×40. (F) RBC count and RDW from complete blood count analysis at autopsy. The mean ± SD and 1-way ANOVA comparison P values are shown.