IM of Flt3^ITD/+mouse HSCs leads to rapid-onset AML. (A) The GrOnc transposon carrying unidirectional gene-activating (Gr1.4 LTR) and bidirectional gene-inactivating or -truncating (βa-SA and En2-SA) elements flanked by repeats for both Sleeping Beauty (SB) and PiggyBac (PB) transposases.¹²  (B) Mouse breeding scheme. (C) Kaplan-Meier survival curves for the different mouse genotypes, showing significantly decreased survival of FTD vs WT control mice (medians, 103 vs 245 days; P = .0001) and of FTD-IM vs WT-IM mice (medians, 73 vs 103 days; P = .009; Mantel-Cox). (D) Of the leukemias in the mice; most were AMLs (81%). (E) Hematoxylin and eosin–stained spleen histology sections from representative control mice and mice with myeloid and lymphoid leukemia, showing splenic effacement in leukemic samples. Bars represent 250 μm. (F) Representative FTD-IM mouse bone marrow sections stained for MPO, B220, and CD3e. Bars represent 100 μm. (G) Blood cell counts and spleen weights in mice with different genotypes. Mice from the 3 experimental cohorts displayed elevated white blood cell counts, reduced platelet counts, and larger spleen sizes compared with controls. **P < .005; ***P < .0005; 1-way analysis of variance. ns, not significant; RBC, red blood cell count; WBC, white blood cell count.