CMPs and GMPs transduced with the combination of Hes1 and BCR-ABL rapidly induced AML/blast crisis of CML. (A) Survival curves of mice. KSLs (n = 5), CMPs (n = 8), and GMPs (n = 5) transduced with the combination of Hes1 and BCR-ABL developed fatal AML/CML in blast crisis-like disease within 18 to 39 days, 20 to 32 days, and 20 to 27 days, respectively. Numbers of injected cells ranged 17 × 10² to 2.6 × 10⁴ for KSLs, 5.5 × 10⁴ to 15 × 10⁴ for CMPs, and 4.0 × 10⁴ to 13.8 × 10⁴ for GMPs. There was no significant difference in latency of penetrance (P < .867). Statistical differences were determined using the log-rank test. Three independent experiments were performed, and the total numbers of transplanted mice are shown. (B) Tissue distribution of the leukemic cells. Mice transplanted with KSLs, CMPs, and GMPs transduced with the combination of Hes1 and BCR-ABL invariably demonstrated marked hepatosplenomegaly and lung hemorrhage, both resulting from infiltration of leukemic cells. (C) The morphology of bone marrow cells from representative recipient mice. Increased myeloid blasts were seen with no significant difference among KSLs, CMPs, and GMPs. (D) Histology of spleen, liver, and lungs from representative mice receiving Hes1⁺BCR-ABL⁺ GMPs. Vast infiltration of leukemic cells is seen. There were no differences in the histology among mice receiving Hes1⁺BCR-ABL⁺ KSLs, CMPs, and GMPs.