Myb deficiency leads to age-related hematological disease. (A) Kaplan-Meier curve showing the percentage survival of a cohort of aging WT and Myb^+/− mice (n = 19 and 17, respectively) over 22 months. Significance was calculated using the log rank test with P = .0035. (B) Pie charts depicting the types of myeloid disease arising with age. (C) Blood smears from diseased mice showing examples of abnormal peripheral blood cells. (i) Target cell erythrocyte (codocyte) (∗). Polychromatic erythrocyte (→). (ii) Teardrop erythrocyte (dacrocyte) (∗). (iii) Micromegakaryocte (∗). (iv) Howell-Jolly body in erythrocytes (∗). Ring-neutrophil (→). Scale bar = 20 μm. (D) Representative sections from tibial bone, spleen, liver, and lung from mice characterized as WT, MPN, MDS, or myeloid leukemia. Scale bars are indicated. (i) Bone section with megakaryocytes (∗) showing an increase in diseased mice. Scale bar = 50 μm. (ii) Spleen sections showing disrupted red and white pulp structure in diseased mice. An example area of white (circle) and red (R) pulp is indicated. Scale bar = 100 μm. (iii) Liver sections showing infiltration of myeloid cells (+). Scale bar = 100 μm (inset: scale bar = 50 μm). (iv) Lung sections showing infiltration of myeloid cells (→). Scale bar = 100 μm. (E) Spleen weight (g) of aging WT and Myb^+/− mice at the point of culling (n = 19 and 17, respectively). Significance was calculated using t test P = .006. Data are represented as the mean and SEM. (F) Ratio of host:donor bone marrow cells from WT (n = 4) and mice with myeloid leukemia (n = 6). Whole bone marrow was transplanted into sublethally irradiated (450 Gy) B6.SJL-Ptprc^a/BoyJ mice. Ratios are calculated by antibody staining of peripheral blood against CD45.1 and CD45.2 antigens at 1, 2, and 3 months after transplant (P = .043, .007, and 0.011, respectively). Data points represent the mean ratios with SEM. SEM, standard error of the mean.