Figure 1.
Figure 1. MYC cooperates with PML-RARα to induce AML. (A) Bone marrow of PML-RARA mice (PR) was transduced with a retrovirus encoding MYC and GFP (MYC) or control retrovirus encoding GFP only (MIG) and introduced into lethally irradiated recipient mice. Combined results from two independent experiments for each group are shown. Median time to AML of 8 PML-RARα + MYC mice was 75 d (1 additional mouse developed T cell acute lymphoblastic leukemia/lymphoma (T-ALL) at 92 d; overall median time to illness 76 d). With longer latencies, some PML-RARα + MIG control retrovirus mice developed leukemia (four mice developed AML, one mouse developed T-ALL, and four mice were euthanized without leukemia or lymphoma). Control FVB/n (Cntr) + MYC mice developed lymphomas with a median latency of 90 d (7 mice developed T-ALL, 2 mice developed lymphoblastic lymphoma in the orbit (injection site), and 1 mouse was euthanized without evidence of leukemia or lymphoma). Differences in leukemia-free survival: PR+MIG versus PR+MYC, P < 0.0001; PR+MYC versus Cntr+MYC, P = NS. (B) Pathology of Cntr + Myc mouse. Results representative of nine lymphomas are shown. (i) Cytology of lymphoblastic cells from the lymph node of mouse #609. Histology of (ii) bone marrow of mouse #34, (iii) thymus of mouse #33, and (iv) liver of mouse #32. (i) Wright’s Giemsa stain. (ii-iv) H&E stain. Bars: (i) 8 µm; (ii) 12 µm; (iii and iv) 60 µm; (iii inset) 24 µm. (C) Immunophenotype of lymphoblastic lymphoma and APL. Splenocytes from a Control + MYC mouse (left; #609) and from a PML-RARα + MYC mouse (right; #608) were stained with the indicated antibodies. Plots are gated on GFP+ cells. Results representative of nine lymphomas and eight leukemias are shown. (D) Pathology of PML-RARα + MYC mouse. Results representative of eight leukemias are shown. (i) Cytology of leukemic cells from spleen of mouse #586. Pathology of (ii) bone marrow of mouse #478, (iii) spleen of mouse #478, and (iv) liver of mouse #478. (i) Wright’s Giemsa stain. (ii-iv) H&E stain. Bars: (i) 8 µm; (ii) 12 µm; (iii and iv) 60 µm; (iii inset) 24 µm.

MYC cooperates with PML-RARα to induce AML. (A) Bone marrow of PML-RARA mice (PR) was transduced with a retrovirus encoding MYC and GFP (MYC) or control retrovirus encoding GFP only (MIG) and introduced into lethally irradiated recipient mice. Combined results from two independent experiments for each group are shown. Median time to AML of 8 PML-RARα + MYC mice was 75 d (1 additional mouse developed T cell acute lymphoblastic leukemia/lymphoma (T-ALL) at 92 d; overall median time to illness 76 d). With longer latencies, some PML-RARα + MIG control retrovirus mice developed leukemia (four mice developed AML, one mouse developed T-ALL, and four mice were euthanized without leukemia or lymphoma). Control FVB/n (Cntr) + MYC mice developed lymphomas with a median latency of 90 d (7 mice developed T-ALL, 2 mice developed lymphoblastic lymphoma in the orbit (injection site), and 1 mouse was euthanized without evidence of leukemia or lymphoma). Differences in leukemia-free survival: PR+MIG versus PR+MYC, P < 0.0001; PR+MYC versus Cntr+MYC, P = NS. (B) Pathology of Cntr + Myc mouse. Results representative of nine lymphomas are shown. (i) Cytology of lymphoblastic cells from the lymph node of mouse #609. Histology of (ii) bone marrow of mouse #34, (iii) thymus of mouse #33, and (iv) liver of mouse #32. (i) Wright’s Giemsa stain. (ii-iv) H&E stain. Bars: (i) 8 µm; (ii) 12 µm; (iii and iv) 60 µm; (iii inset) 24 µm. (C) Immunophenotype of lymphoblastic lymphoma and APL. Splenocytes from a Control + MYC mouse (left; #609) and from a PML-RARα + MYC mouse (right; #608) were stained with the indicated antibodies. Plots are gated on GFP+ cells. Results representative of nine lymphomas and eight leukemias are shown. (D) Pathology of PML-RARα + MYC mouse. Results representative of eight leukemias are shown. (i) Cytology of leukemic cells from spleen of mouse #586. Pathology of (ii) bone marrow of mouse #478, (iii) spleen of mouse #478, and (iv) liver of mouse #478. (i) Wright’s Giemsa stain. (ii-iv) H&E stain. Bars: (i) 8 µm; (ii) 12 µm; (iii and iv) 60 µm; (iii inset) 24 µm.

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