Loss of Utx accelerates leukemia development in a NOTCH1-induced T-ALL mouse model. (A) Graphical illustration of NOTCH1-induced T-ALL mouse model. Fetal liver cells are partially transduced with vectors encoding NOTCH1 (ICN) (coexpressing mCherry), and the shRNA or empty vector control (coexpressing GFP), followed by tail vein injection in lethally irradiated mouse recipients and monitoring of leukemia onset. (B) Kaplan-Meier curves and log-rank (Mantel-Cox) analysis show accelerated leukemia onset in Utx sh#1 (n = 7, P < .0001) (blue) and Utx sh#3 (n = 4, P = .02) (red) mice as compared with empty vector (n = 14) (black) mouse recipients. (C) Western blot analysis of Utx and H3K27me3 in a representative Utx sh#1 mouse leukemia sample. Utx protein levels and H3K27me3 levels are quantified by Image J, normalized to tubulin levels, and compared with expression levels in control mice. (D) Immunophenotypical fluorescence-activated cell sorter analysis of CD4 and CD8 T-cell markers in the Utx sh#1, Utx sh#3, and empty vector control mouse leukemias. A representative example of each subtype is depicted.