Tet2^−/−mice evolved to lethal myeloid malignancies. (A) Kaplan-Meier survival curve of WT (n = 48), Tet2^+/− (n = 66), and Tet2^−/− (n = 62) mice up to 1 year of age. (B) Appearance of a representative moribund Tet2^−/− mouse (2A48) with distended abdomens (i) and pale footpads (ii), the gross morphology of spleen (iii), and liver (iv) of this moribund Tet2^−/− mice are drastically different from WT control. (C) Spleen and liver weights of moribund/deceased Tet2^−/− (n = 18) and Tet2^+/− (n = 5) mice as well as age matched WT controls. (D) H&E staining of paraffin-embedded sections of spleen, liver, and femurs from representative deceased/moribund Tet2^−/− (2A116, 2A57, 2A45, 2A19) and Tet2^+/− (2A102) mice. (E) May-Giemsa–stained BM cytospin-preparations from representative deceased/moribund Tet2^−/− (2A116, 2A45, 2A19) or Tet2^+/− (2A102) mice. (F) Lineage distribution of BM and spleen cells of representative deceased/moribund Tet2^−/− (2A116, 2A57, 2A45) and Tet2^+/− (2A102) mice. (G) Flow cytometric analysis of monocytic lineages in representative deceased/moribund Tet2^−/− (3G53) and Tet2^+/− (2A102) mice. (H) Flow cytometric analysis of LSK (Lin^–Sca-1⁺Kit⁺) and LK (Lin^–Sca-1⁻Kit⁺) cell population in representative deceased/moribund Tet2^−/− (2A19 and 2A116) and Tet2^−/− (2A102) mice. The numbers indicate the percentages of cells in each cell population. ***P < .001.