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. Author manuscript; available in PMC: 2011 May 18.
Published in final edited form as: Cancer Cell. 2010 May 18;17(5):455–468. doi: 10.1016/j.ccr.2010.03.022

Figure 4. Acute myeloid leukemia development in Cbfb+/MYH11d179-221 and Cbfb+/MYH11 chimeras.

Figure 4

(A) Survival curves of Cbfb+/MYH11d179-221 and Cbfb+/MYH11 chimeras. Dotted line: the survival curve of Cbfb+/MYH11 chimeras (n=17); solid line: the survival curve of Cbfb+/MYH11d179-221 chimeras (n=22). The mice were not treated with any mutagens such as ENU.

(B) Morphology of leukemic cells in the Cbfb+/MYH11d179-221 mice. Left panel: wright-Giemsa stained peripheral blood smears showing poorly differentiated stem cell like cells (arrowheads) and myeloblasts (arrows). Middle and right panels: H&E stained bone marrow sections from mice of the indicated genotypes. Scale bar in the left panel represent 10 μm; those in the middle and right panels represent 50 μm.

(C) FACS analysis of peripheral blood cells in a Cbfb+/MYH11d179-221 mouse using antibodies against c-kit, Mac-1, GR-1, CD131, B220, CD4 and CD8.

(D) Correlation between cell morphology and surface marker expression for leukemic cells from the Cbfb+/MYH11d179-221 mice. FACS sorted c-kit+/GR1−/Mac1− and c-kit−/GR1+/Mac1+ populations from mice of the indicated genotypes were analyzed for morphologic features through Wright-Giemsa staining of cytospin preparations. Scale bars represent 10 μm.

(E) The percentages of leukemia cells expressing c-kit or Gr-1/Mac1 in the Cbfb+/MYH11 and Cbfb+/MYH11d179-221 mice (N = 5 for each genotype) as detected by FACS. The error bars represent one standard deviation.

(F and G) Expression of the knocked-in fusion genes in the leukemia cells. (F) RT-PCR with RNA samples from ES cells (lanes 1–4) and leukemic cells (lanes 5–7) with PCR primers flanking the Cbfb and MYH11 fusion junctions in Cbfb-MYH11 and Cbfb-MYH11d179-221. Lane 1: ES cell line TC1; Lane 2: ES cell clone #10 with knock-in of Cbfb-MYH11; Lanes 3 and 4: ES cell lines #220 and 269 with knock-in of Cbfb-MYH11d179-221; Lane 5: leukemia cells from a Cbfb+/MYH11 chimera; Lanes 6 and 7: leukemia cells from two Cbfb+/MYH11d179-221 chimeras. (G) Western blot analysis with protein samples from leukemic cells of the indicated genotype and the CBFβ-specific antibody (β141.2).