Figure 2. NUP98-fusion-protein-driven AML is highly dependent on sustained oncoprotein expression in vivo .

(a) Schematic illustration of the experimental workflow to induce downregulation of oncogene expression in vivo. 1x10⁶ GFP/CD45.2-positive leukemia cells were transplanted into sublethally irradiated secondary recipients. Animals were treated with Dox (4 mg/ml) after an engraftment period of 15 days. (b) Representative bioluminescence imaging of untreated vs. Dox-treated mice transplanted with NUP98/NSD1-expressing leukemia cells. (c) Kaplan-Meier survival curves of mice transplanted with leukemia cells expressing indicated NUP98-fusion proteins receiving either no treatment or Dox (4 mg/ml) (n ≥ 4). (d-e) Flow cytometric analyses of bone-marrow-derived leukemia at indicated time points after Dox treatment of mice (mean ± s.d. n = 3). (d) Quantification of mean fluorescence intensity (MFI) of GFP. (e) Quantification of the myeloid differentiation markers Mac-1/Gr-1 and the progenitor cell marker c-Kit. (f) Representative cytospin images of untreated vs. Dox-treated (8 days) NUP98/JARID1A-expressing cells in vitro.