The leukemias derived from FLT3/ITD-NHD13 mice are driven by FLT3/ITD signaling with frequent loss of the WT Flt3 allele. (A) PCR for a region of Flt3 encompassing the ITD mutation. Leukemic bone marrow, liver, and spleen compared with control tail DNA to assay for loss of the WT Flt3 allele. (B) Loss of heterozygosity in sorted HSPC populations. (Ci) Transplant recipients treated with either sorafenib or vehicle for 4 weeks. Percent engraftment as ratio of CD45.2/CD45.1 in peripheral blood at 2 weeks and 4 weeks after initiation of sorafenib treatment. (Cii-iii) Example of peripheral blood stained to evaluate for the presence of blasts in mice treated with vehicle or sorafenib for 1 month. (D) Primary leukemic cells treated in vitro with either 10nM or 20nM sorafenib and probed for phosphorylation of FLT3, STAT5, AKT, and MAPK along with total protein of each. (E) Gene expression profiling for Flt3 and Meis1 in 10 NHD13 alone mice developing AML.