MYC mutants cooperate with PML-RARα to induce AML. (A) Bone marrow of PML-RARA (PR) or control FVB/n (Cntr) mice was transduced with a retrovirus encoding MYC^T58A and introduced into lethally irradiated recipient mice. Combined results from two independent experiments for each group are shown. Median time to APL of 10 PML-RARα + MYC^T58A mice was 70 d. Control FVB/n + MYC^T58A mice developed AML (5 mice), T-ALL (3 mice), or were euthanized without evidence of leukemia or lymphoma (2 mice). Median time to disease was 101 d. Difference in leukemia-free survival: P < 0.0001. (B) Bone marrow of PML-RARA (PR) or control FVB/n (Cntr) mice was transduced with a retrovirus encoding MYC with a deletion of the MBII domain (MYC^ΔMBII) and introduced into lethally irradiated recipient mice. Combined results from two independent experiments for each group are shown. Median time to APL of 10 PML-RARα + MYC^ΔMBII mice was 92 d. Control FVB/n + MYC^ΔMBII mice developed T-ALL (four mice) or were euthanized without evidence of leukemia or lymphoma (six mice). Difference in leukemia-free survival: P < 0.0001.