In vivo modeling of erythroid transformation by aberrant SKI expression. (A) Experimental design: hematopoietic stem cells (HSC), granulocyte-monocyte progenitors (GMP), and megakaryocyte-erythroid progenitors (MEP) were sorted from WT mice, retrovirally transduced with SKI or an empty vector (Ctrl) carrying an IRES-GFP expression cassette, and injected into lethally irradiated recipients. (B) Left, GFP⁺ cells (percentage) in the BM of transplanted mice. Mean plus or minus SD is shown (n = 5 per group). Right, Kaplan-Meier plot of disease symptoms in transplanted mice. Only mice transplanted with SKI-transduced HSCs and MEP developed disease. (C) Flow cytometry analysis of myeloid cells (CD11b⁺Gr-1⁺), erythroid progenitors (CD71⁺Ter119⁺), B cells (B220⁺), and T cells (CD4⁺CD8⁺) gated for viable GFP⁺ cells, in spleens of mice transplanted with HSC (Ctrl vs SKI) or MEP (SKI) cells. (D) Percentage of myeloid cells (CD11b⁺Gr1⁺), erythroid progenitors (CD71⁺Ter119⁺), B cells (B220⁺), and T cells (CD4⁺CD8⁺) within viable GFP⁺ cells, in HSC-Control (Ctrl), HSC-SKI, and MEP-SKI in primary mice BM and spleen. Mean plus or minus SD is shown (n = 5 per group). (E) Number of GFP⁺ and GFP⁻ total BM cells, myeloid cells (CD11b⁺Gr1⁺), and erythroid progenitors (CD71⁺Ter119⁺) in the BM of diseased primary recipients. Mean plus or minus SD is shown (n = 5 per group). (F) Flow cytometry analysis of terminal erythroid differentiation in the BM of diseased HSC (Ctrl and SKI) and MEP-SKI recipients, determined by forward scatter (FSC-A) and CD44 expression gated for viable Ter119⁺ cells. Bottom panel, Mean plus or minus SD (n = 5 per group) of the percentage of each population. (G) Histopathology analysis of BM spleen and liver of mice transplanted with HSC-Ctrl (left row) or HSC-SKI (right row) stained with hematoxylin-eosin (top 6 photomicrographs; original magnification ×20) or with a GATA1 antibody (bottom 4 photomicrographs; original magnification ×20).