Figure 3.
Figure 3. Inhibition of apoptosis with Bcl-2 is required for development of lymphoid but not myeloid leukemias. (A) Kaplan-Meier survival analysis of bone marrow transplants using MSCV-Bcl2, MSCV-Myc, and MSCV-Myc+Bcl2 using wild-type Balb/c donors and recipients. (B) Flow cytometric analysis of bone marrow cells from animals that underwent transplantation. Samples from MSCV-Myc and MSCV-Myc+Bcl2 mice were isolated from moribund animals. MSCV-Bcl2 mice never appeared ill and were killed as controls 5 months after marrow transplantation. Compared with MSCV-Bcl2 mice, both MSCV-Myc and MSCV-Myc+Bcl2 mice have a large Gr-1+/Mac1+ blast population. MSCV-Myc mice also show a population of cells pseudo-positive for both B220 and CD3. These cells were judged apoptotic cells as judged by annexin V and 7-AAD staining, morphology, and failure to give disease in secondary transplant recipients (not shown). (C) Flow cytometric analysis of thymocytes from the same leukemic and control animals. MSCV-Myc+Bcl2 mice show an increase in B220+/IgM- early B cells in the thymus whereas MSCV-Myc mice show a relative loss of mature single-positive thymocytes. (D, E) Flow cytometric analysis of lymph node cells isolated from MSCV-Myc+Bcl2, MSCV-Myc, and MSCV-Bcl2 animals. Both MSCV-Bcl2 and MSCV-Myc mice have a near-normal complement of B and T cells. (D) Immunophenotype of lymph node cells of mice that underwent transplantation. B220+ cells predominate in MSCV-Myc+Bcl2 mice at the expense of CD3+ T cells. (E) Lymph node cells in MSCV-Myc+Bcl2 mice are immature B lymphoblasts (CD43+, IgM-). In contrast, lymph node cells from MSCV-Myc and MSCV-Bcl2 mice are a mixture of mature B cells (CD43-, IgM+) and mature T cells (CD4 and CD8 single-postive cells). (F) Histopathologic analysis of hematopoietic tissues from MSCV-Myc+Bcl2, MSCV-Myc, and MSCV-Bcl2 mice. MSCV-Myc+Bcl2 mice have myeloid blast cells in the bone marrow and lymphoid blast cells in the lymph node and thymus. MSCV-Myc mice have myeloid blast cells in the bone marrow, mostly mature lymphocytes in the lymph nodes, with some invading myeloid blasts, and normal-appearing thymocytes in the thymus. MSCV-Bcl2 mice have mature-appearing, apparently normal cells in the bone marrow, lymph nodes, and thymus.

Inhibition of apoptosis with Bcl-2 is required for development of lymphoid but not myeloid leukemias. (A) Kaplan-Meier survival analysis of bone marrow transplants using MSCV-Bcl2, MSCV-Myc, and MSCV-Myc+Bcl2 using wild-type Balb/c donors and recipients. (B) Flow cytometric analysis of bone marrow cells from animals that underwent transplantation. Samples from MSCV-Myc and MSCV-Myc+Bcl2 mice were isolated from moribund animals. MSCV-Bcl2 mice never appeared ill and were killed as controls 5 months after marrow transplantation. Compared with MSCV-Bcl2 mice, both MSCV-Myc and MSCV-Myc+Bcl2 mice have a large Gr-1+/Mac1+ blast population. MSCV-Myc mice also show a population of cells pseudo-positive for both B220 and CD3. These cells were judged apoptotic cells as judged by annexin V and 7-AAD staining, morphology, and failure to give disease in secondary transplant recipients (not shown). (C) Flow cytometric analysis of thymocytes from the same leukemic and control animals. MSCV-Myc+Bcl2 mice show an increase in B220+/IgM- early B cells in the thymus whereas MSCV-Myc mice show a relative loss of mature single-positive thymocytes. (D, E) Flow cytometric analysis of lymph node cells isolated from MSCV-Myc+Bcl2, MSCV-Myc, and MSCV-Bcl2 animals. Both MSCV-Bcl2 and MSCV-Myc mice have a near-normal complement of B and T cells. (D) Immunophenotype of lymph node cells of mice that underwent transplantation. B220+ cells predominate in MSCV-Myc+Bcl2 mice at the expense of CD3+ T cells. (E) Lymph node cells in MSCV-Myc+Bcl2 mice are immature B lymphoblasts (CD43+, IgM-). In contrast, lymph node cells from MSCV-Myc and MSCV-Bcl2 mice are a mixture of mature B cells (CD43-, IgM+) and mature T cells (CD4 and CD8 single-postive cells). (F) Histopathologic analysis of hematopoietic tissues from MSCV-Myc+Bcl2, MSCV-Myc, and MSCV-Bcl2 mice. MSCV-Myc+Bcl2 mice have myeloid blast cells in the bone marrow and lymphoid blast cells in the lymph node and thymus. MSCV-Myc mice have myeloid blast cells in the bone marrow, mostly mature lymphocytes in the lymph nodes, with some invading myeloid blasts, and normal-appearing thymocytes in the thymus. MSCV-Bcl2 mice have mature-appearing, apparently normal cells in the bone marrow, lymph nodes, and thymus.

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