Effect of C/EBPε-ER on differentiation of myeloid leukemia in vivo.

PML-RARα leukemia no. 1111 was transduced with retroviruses expressing only GFP (MIG) or hC/EBPε-ER^TM, and 25 000 sorted GFP⁺ cells were injected intravenously into sublethally irradiated FVB/N mice. The leukemic cells were allowed to engraft and expand. Beginning on day 27, 4-HT or vehicle was administered daily by intraperitoneal injection. The MIG recipient animals became moribund and were killed on day 30. The hC/EBPε-ER^TM recipient animals were killed on day 31. (A) Bone marrow smears of recipients of MIG- and hC/EBPε-ER^TM–transduced cells either with or without 4-HT treatment. Wright Giemsa stain was used, and images were captured with × 40 objectives. (B) Surface-marker expression of CD11b (Mac-1) in MIG or C/EBPε-ER^TM recipients. Histograms were gated on live (based on FSC and SSC) GFP⁺ cells. The solid graph represents vehicle treatment, and the black line represents 4-HT treatment. (C) Differential counts (200 cells) of bone marrow smears of individual recipients of control or C/EBPε-ER^TM–transduced cells, treated as indicated. Immature indicates immature forms or blasts; intermediate, intermediate forms; mature, mature neutrophilic cells; other, erythroid cells, lymphocytes, and eosinophils.