Figure 1.
Figure 1. MSCV-Myc induces myeloid and lymphoid disease phenotypes simultaneously in Ink4a-/- mice, and myeloid leukemia exclusively in Ink4a+/+ mice. (A) Kaplan-Meier survival analysis of mice that underwent transplantation with Ink4a+/+ or Ink4a-/- bone marrow. GFP indicates MSCV-GFP; Myc, MSCV-Myc; Ink, Ink4a. Mice reconstituted with Ink4a-/- bone marrow transduced with GFP (GFP/Ink-/-) were free of disease. Median survival of Myc→Ink4a-/- reconstituted mice was 28 days, and that of Myc→Ink4a+/+ mice was 62 days. (B) Flow cytometric analysis of bone marrow cells from Myc→Ink4a+/+ and Myc→Ink4a-/- mice. Bone marrow data from GFP→Ink4a+/+ mice are shown as controls. GFP-positive cells from Ink4a-/- mice show two populations of leukemic cells: a Mac-1+/Gr-1+ myeloid population, and a B220+/CD3- lymphoid population. In Ink4a+/+ mice, there is only a single Mac-1+/Gr-1+ myeloid population. (C) Flow cytometric analysis of lymph node cells from Myc→Ink4a+/+ and Myc→Ink4a-/- mice. Lymph node cells from GFP→Ink4a+/+ mice are shown as controls. Myc→Ink4a-/- mice show a single GFP-positive population with a B-lymphoid immunophenotype (Mac-1-/Gr-1-, and B220+/CD3-). Lymph node cells from Myc→Ink4a+/+ mice show two populations of cells, a GFP-low and a GFP-high population. The GFP-high cells are Mac-1+/Gr-1+ myeloid cells, and the GFP-low cells are a mixture of B220+ B lymphocytes and CD3+ T lymphocytes similar to those seen in lymph nodes of control GFP→Ink4a+/+ mice. (D) Further immunophenotyping of lymph node cells from leukemic mice. IgM and CD43 staining reveals that lymphoid cells from Myc→Ink4a-/- mice are immature (IgM-/CD43-low) B-lineage cells, in contrast to lymph node cells from Myc→Ink4a+/+ mice and GFP→Ink4a+/+ mice, which are a mixture of mature IgM+ B cells and T cells that are CD3+. (E) Cell morphology. Myc→Ink4a-/- mice show a mixture of myeloid and lymphoid blast cells in the bone marrow (BM), and lymphoid blasts in the lymph nodes (LN) and thymus (Thy). Myc→Ink4a+/+ mice show only myeloid blasts in the bone marrow and lymph nodes, and normal-appearing cells in thymus.

MSCV-Myc induces myeloid and lymphoid disease phenotypes simultaneously in Ink4a-/-mice, and myeloid leukemia exclusively in Ink4a+/+mice. (A) Kaplan-Meier survival analysis of mice that underwent transplantation with Ink4a+/+ or Ink4a-/- bone marrow. GFP indicates MSCV-GFP; Myc, MSCV-Myc; Ink, Ink4a. Mice reconstituted with Ink4a-/- bone marrow transduced with GFP (GFP/Ink-/-) were free of disease. Median survival of Myc→Ink4a-/- reconstituted mice was 28 days, and that of Myc→Ink4a+/+ mice was 62 days. (B) Flow cytometric analysis of bone marrow cells from Myc→Ink4a+/+ and Myc→Ink4a-/- mice. Bone marrow data from GFP→Ink4a+/+ mice are shown as controls. GFP-positive cells from Ink4a-/- mice show two populations of leukemic cells: a Mac-1+/Gr-1+ myeloid population, and a B220+/CD3- lymphoid population. In Ink4a+/+ mice, there is only a single Mac-1+/Gr-1+ myeloid population. (C) Flow cytometric analysis of lymph node cells from Myc→Ink4a+/+ and Myc→Ink4a-/- mice. Lymph node cells from GFP→Ink4a+/+ mice are shown as controls. Myc→Ink4a-/- mice show a single GFP-positive population with a B-lymphoid immunophenotype (Mac-1-/Gr-1-, and B220+/CD3-). Lymph node cells from Myc→Ink4a+/+ mice show two populations of cells, a GFP-low and a GFP-high population. The GFP-high cells are Mac-1+/Gr-1+ myeloid cells, and the GFP-low cells are a mixture of B220+ B lymphocytes and CD3+ T lymphocytes similar to those seen in lymph nodes of control GFP→Ink4a+/+ mice. (D) Further immunophenotyping of lymph node cells from leukemic mice. IgM and CD43 staining reveals that lymphoid cells from Myc→Ink4a-/- mice are immature (IgM-/CD43-low) B-lineage cells, in contrast to lymph node cells from Myc→Ink4a+/+ mice and GFP→Ink4a+/+ mice, which are a mixture of mature IgM+ B cells and T cells that are CD3+. (E) Cell morphology. Myc→Ink4a-/- mice show a mixture of myeloid and lymphoid blast cells in the bone marrow (BM), and lymphoid blasts in the lymph nodes (LN) and thymus (Thy). Myc→Ink4a+/+ mice show only myeloid blasts in the bone marrow and lymph nodes, and normal-appearing cells in thymus.

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