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. 2020 Jun 10;1(1):82–95. doi: 10.1158/2643-3230.BCD-19-0080

Figure 6.

Figure 6. Effects of lipids and inhibitors of SREBF1 activation on the expression of MEF2D-fusion protein and the therapeutic efficacies of inhibitors. A, Incubation of MEF2D-ALL cells with cholesterol diminished the expression of MEF2D-fusion protein. Cells were cultured in the presence (+) or absence (−) of cholesterol (10 μg/mL cholesterol and 2 μg/mL 25-hydroxycholesterol) for 3 days. Expression of the indicated proteins was analyzed by Western blotting. B, Treatment of five MEF2D-ALL cell lines with fatostatin, FGH10019, and betulin reduced the protein expression of MEF2D-fusion and SREBF1. Cells were treated with fatostatin (3 μmol/L), FGH10019 (3 μmol/L), or betulin (10 μmol/L) for 3 days. All treatments reduced SREBF1 expression. + and – denote treatment with the indicated drug and vehicle, respectively. C, Treatment of Kasumi-7 cells with the indicated inhibitors of SREBF1 activation, as in B, reduced the expression of BCL6, FOS, and EGR1. D, Fatostatin, FGH10019, and betulin selectively inhibited MEF2D-ALL cell growth. Cells were treated with varying concentrations of the drugs for 3 days as indicated. Cell growth was monitored and compared with vehicle treatment as a control. The values relative to the control are presented as means ± SDs (n = 3). E, FGH10019 retards Kasumi-7 cell growth and prolongssurvival in mice. Immunodeficient mice were transplanted with Kasumi-7 cells engineered to express GFP and subsequently treated with FGH10019 (25 mg/kg/day, 6 days per week) or vehicle (n = 5 each). Peripheral blood was collected at 8 and 11 weeks after transplantation and analyzed to determine the %GFP-expressing cells (left). The difference in %GFP between samples from FGH10019- and vehicle-treated mice was statistically significantly different (Wilcoxon rank-sum test; top right). The estimated Kaplan–Meier survival curves of FGH10019- and vehicle-treated mice were also statistically significantly different (log-rank test; bottom right). F, Pre-BCR expression in the indicated cells after treatment with FGH10019 (3 μmol/L) or vehicle for 3 days in culture.

Effects of lipids and inhibitors of SREBF1 activation on the expression of MEF2D-fusion protein and the therapeutic efficacies of inhibitors. A, Incubation of MEF2D-ALL cells with cholesterol diminished the expression of MEF2D-fusion protein. Cells were cultured in the presence (+) or absence (−) of cholesterol (10 μg/mL cholesterol and 2 μg/mL 25-hydroxycholesterol) for 3 days. Expression of the indicated proteins was analyzed by Western blotting. B, Treatment of five MEF2D-ALL cell lines with fatostatin, FGH10019, and betulin reduced the protein expression of MEF2D-fusion and SREBF1. Cells were treated with fatostatin (3 μmol/L), FGH10019 (3 μmol/L), or betulin (10 μmol/L) for 3 days. All treatments reduced SREBF1 expression. + and – denote treatment with the indicated drug and vehicle, respectively. C, Treatment of Kasumi-7 cells with the indicated inhibitors of SREBF1 activation, as in B, reduced the expression of BCL6, FOS, and EGR1. D, Fatostatin, FGH10019, and betulin selectively inhibited MEF2D-ALL cell growth. Cells were treated with varying concentrations of the drugs for 3 days as indicated. Cell growth was monitored and compared with vehicle treatment as a control. The values relative to the control are presented as means ± SDs (n = 3). E, FGH10019 retards Kasumi-7 cell growth and prolongssurvival in mice. Immunodeficient mice were transplanted with Kasumi-7 cells engineered to express GFP and subsequently treated with FGH10019 (25 mg/kg/day, 6 days per week) or vehicle (n = 5 each). Peripheral blood was collected at 8 and 11 weeks after transplantation and analyzed to determine the %GFP-expressing cells (left). The difference in %GFP between samples from FGH10019- and vehicle-treated mice was statistically significantly different (Wilcoxon rank-sum test; top right). The estimated Kaplan–Meier survival curves of FGH10019- and vehicle-treated mice were also statistically significantly different (log-rank test; bottom right). F, Pre-BCR expression in the indicated cells after treatment with FGH10019 (3 μmol/L) or vehicle for 3 days in culture.