Myc-induced myeloid leukemias are characterized by increased bone marrow apoptosis. (A) Apoptotic cells in the bone marrow of moribund leukemic mice were assessed by annexin V and 7-AAD staining and followed by flow cytometry. Numbers represent the percentage of events in each quadrant. MSCV-Myc+Bcl2 (MiB)/Balb/c showed 15% annexin V- and/or 7-AAD-positive cells compared with 38% dying cells in matched stain mice expressing Myc but not Bcl-2 (Myc/Balb, top panels). Bone marrow from leukemic Myc/Ink4a^-/- mice are 5% apoptotic compared with 29% apoptotic cells in the marrow of wild-type mice expressing Myc (Myc/Ink4a^+/+, bottom panels). A representative of 3 independent analyses is shown. (B) Bone marrow sections from moribund leukemic mice were prepared and stained with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). Myc induces AML and apoptosis, whereas Myc+Bcl2 induces AML and ALL. Expressing Myc in bone marrow with targeted disruption of the Ink4a gene (Ink4a^-/-) yields results similar to Myc+Bcl2. MiB, MSCV-Myc+Bcl2; Myc, MSCV-Myc; Ink, Ink4a.