Runx2 cooperates with Cbfβ-SMMHC to induce AML in mice. (A) Depiction of Runx2 transcripts identified in leukemia cells with retrovirus insertions in the intron 5 of Runx2 (arrowheads), the full-length Runx2, and various truncated Runx2 (RT1, RT2, RT3) constructs used in this study. The coding (gray boxes) and noncoding (open boxes) exons, and distal (P1) and proximal (P2) promoters (arrows) are shown on top. The transcripts isolated from leukemic samples for the full-length (Runx2) and truncated RT1, RT2, and RT3 transcripts, including indicated exons (gray lines) and viral sequences (black lines). (B) Western blot analysis showing the expression of full-length Runx2 (lane 1), RT1 (lane 2), and RT-2 (lane 3) from the expression constructs used. (C) BM transduction transplantation strategy for validation of Runx2 oncogenic function. BM progenitors from wild-type or Cbfb-MYH11 (CM) expressing mice were infected with MIG retrovirus and transplanted into irradiated isogenic recipients. Statistical significance was performed using the log-rank test. (D) Kaplan-Meier survival curve of Runx2/CM (n = 22), RT1/CM (n = 12), RT2/CM (n = 10), RT3/CM (n = 8) or mock/CM (n = 24), and Runx2 (n = 11), RT1 (n = 6), RT2 (n = 6), RT3 (n = 6) or mock (n = 6) in wild-type cells. Analysis of statistical significance was performed using the log-rank test. (E) Kaplan-Meier survival curve depicting the role of Runx2 heterozygosity in Cbfβ-SMMHC-mediated leukemogenesis. Test groups included Cbfb^+/56MMx1Cre Runx2^+/+ mice expressing Cbfb-MYH11 (CM; n = 28), Cbfb^+/56MMx1CreRunx2^+/− (CM/Rx2^+/−, n = 34), and Cbfb^+/56MMx1CreRunx2^+/dC (CM/RdC; n = 46). Control groups included pIpC-treated Cbfb^+/56M (control; n = 15) and untreated Cbfb^+/56M/Mx1Cre (control, n = 15) mice. Analysis of statistical significance was performed using the log-rank test.