Figure 2.
Acute myeloid leukemias induced by MLL-ENL from stem and progenitor cells. (A) The extent of engraftment and development of AML was monitored by FACS analysis of GFP+ cells in peripheral blood mononuclear cells (PBMC). Mice (five per cohort) were transplanted with 1000 HSC transduced with control (blue line) or ME (dashed line) retroviruses, or with 10,000 ME-transduced CMP (black line), GMP (dotted line), or MEP (red line). Mice transplanted with control-transduced CMP, GMP, or MEP did not show any donor-derived Ly5.2+ cells after 6 to 7 wk posttransplantation (data not shown). (B-C) AML in preterminally leukemic mice. (B) Liver histology showing massive blast invasion in recipients of ME-transduced stem and progenitor cells. (C) May-Grünwald-Giemsa staining of splenocytes, indicating mostly blast and myelomonocytic morphologies. (D-E) Chimera analysis in mice 9 wk after transplantation of transduced stem and progenitor populations. ACK-treated bone marrow cells were analyzed for expression of GFP, Ly5.2 (donor-derived), and various myeloid (Mac-1, Gr-1) and lymphoid (CD19, TCRβ) markers. (D) An expanded population of ME-transduced donor-derived GFP+ cells is present in all leukemic mice. (E) ME-transduced GFP+ donor-derived cells only expressed myeloid markers (Mac-1high, Gr-1-/low) in contrast to multilineage readout of control-transduced HSC. (F) Multilineage reconstitution from untransduced GFP- donor-derived cells in ME-transduced HSC reconstituted mice. Consistent with their transient repopulating ability, untransduced GFP- donor-derived cells are not detected in CMP or GMP transplanted mice, confirming the absence of HSC contamination in the transplant.