I-BET151 inhibits MLL-fusion leukemic cell lines, patient-derived cells and cord blood models <i>in vitro</i> and <i>in vivo</i>.

<p><b>A</b>) Percentage of Annexin V positive cells after 72 hours incubation with DMSO or I-BET151 in different concentrations (technical triplicate ± s.d of 3 independent experiments) for different human leukemia cell lines. <b>B</b>) FACS analysis of Annexin V positive cells after 72 h incubation with DMSO or 1 μM I-BET151. <b>C</b>) Growth curves for immortalized CB MLL-AF9 MS5 co-cultures (myeloid and lymphoid conditions), normal CB CD34⁺ cells and patient derived CB MLL-AF9 (AML#1) upon I-BET151 treatment. Arrows indicate treatment. For CB transductions, demi-depopulated cells were analysed by flow and all cells were GFP⁺ and cell counts reflect MLL-AF9⁺ CB cells. <b>D</b>) Growth curves for immortalized CB MLL-AF9 myeloid cells in MS5 co-culture and liquid condition. Data were normalized to 100% relative to the response of DMSO treated cells. I-BET151 was added at every indicated time point. <b>E</b>) Percentage of Annexin V positive cells after 72 h incubation with DMSO or I-BET151 in different concentrations (technical triplicate ± s.d of 3 independent experiments) for CB transduced MLL-AF9 in liquid or MS5 co-culture setting. <b>F</b>) CB MLL-AF9 cells were transplanted into human Scaffold mice after which mice were treated with I-BET151 and pictures depict tumors in control groups and 500uM I-BET151 treated groups. <b>G</b>) Experiment as in H, and tumor volumes were measured by caliper during the course of the experiment.