Mll^PTD/WT:Flt3^ITD/WT mice develop a predominance of AML. (A) Frequencies of acute leukemia immunophenotypes identified in Mll^PTD/WT:Flt3^ITD/WT mice (n = 33). (B) Representative flow cytometry plots from spleen and BM samples from age-matched controls and moribund Mll^PTD/WT:Flt3^ITD/WT mice killed with elevated WBC counts. AML with maturation (myeloperoxidase [MPO⁺]/CD3⁻/CD19⁻/B220⁻/CD11b⁺/Gr1⁺/CD117⁻; 15%), AML without maturation group A (MPO⁺/CD3⁻/B220^lo/CD19⁻/CD11b^lo/−/Gr1⁻/CD117^+/−; 34%), AML without maturation group B (MPO⁺/CD3⁻/B220⁺/CD19⁻/CD11b^+/−/Gr1⁻/CD117^+/−; 21%). Regions highlighted in the red rectangle emphasize key differences in populations for each of the AML immunophenotypes. MPO staining by IHC and flow cytometry results for B-cell and biphenotypic leukemias are not shown. (C) WBC counts of leukemic Mll^PTD/WT:Flt3^ITD/WT mice are significantly elevated at the time of death. Figure shows WBC counts from 3 age-matched cohorts of Mll^PTD/WT:Flt3^ITD/WT mice with AML and controls. (D) Mll^PTD/WT:Flt3^ITD/WT mice with leukemia exhibit significant splenomegaly at the time of death. Figure shows weights from 3 age-matched cohorts of Mll^PTD/WT:Flt3^ITD/WT mice with AML and controls. (E) Representative image of spleens from a Mll^PTD/WT:Flt3^ITD/WT mouse dying of AML with age-matched controls. (F) Representative blood smear stained with Wright-Giemsa and hematoxylin and eosin-stained organ preparations from a Mll^PTD/WT:Flt3^ITD/WT mouse dying of AML. Micrographs demonstrate blasts in peripheral blood (original magnification ×1000) and extensive infiltrations of myeloid blasts in liver (original magnification ×400), and adrenal gland (original magnification ×400). Micrograph images were recorded using a Zeiss Axioskop, Olympus Magnafire digital camera, using a 10× eyepiece, 40×/0.65 NA Acroplan objective lens or 100×/1.40 NA Plan-Apochromat and Zeiss Axiovision Version 4.7.2 software.