In vivo lymphoid and myeloid leukemia model. (A) Left: Schematic representation of the experimental setup. Oncogene-expressing HPC^LSK cell lines were injected IV in NSG recipients, and moribund mice were analyzed. Healthy HPC^LSK injected animals were sacrificed and examined after 150 days. Right: Disease-free survival following IV injection of 2 × 10⁶ HPC^LSK BCR/ABL^p210 (n = 9), or 5 × 10⁶ HPC^LSK MLL-AF9 (n = 7), HPC^LSK Flt3-ITD;NRas^G12D (n = 5), and HPC^LSK BCR/ABL^p185 (n = 9) cells compared with injection of 5 × 10⁶ untransformed HPC^LSK cells (n = 5). (B) WBC count of moribund mice, 1-way analysis of variance (Kruskal-Wallis test) with Dunn's multiple comparison test, *P <.05. Data are presented as mean ± SEM. (C) Detection of transformed GFP⁺ HPC^LSK cells (with the respective oncogene) in blood, spleen, and BM of diseased NSG recipients. Data represent mean ± SD in 4 to 8 mice per group. (D) Top: Representative blood smears from transformed HPC^LSK-injected mice show leukocytosis with circulating blasts (hematoxylin-eosin, original magnification ×400). Bottom: Macroscopic view of representative spleens from transformed HPC^LSK-injected recipient mice compared with untransformed HPC^LSK-injected mice, n ≥ 5. Scale bar, 1 cm. (E) Left: Quantification of transformed GFP⁺ LSKs and differentiated cells (CD19⁺ B cells and CD11b⁺ myeloid cells) by flow cytometry in spleens of diseased NSG recipient mice. Error bars represent the mean ± SD, n = 4 to 8 per oncogene. Right: Representative flow cytometry plots for myeloid (CD11b and Gr-1) and lymphoid (CD19 and CD3 or B220) cells of spleens of the diseased mice injected with different oncogene-expressing HPC^LSKs.