Figure 2. EPZ004777 Inhibits Cellular H3K79 Methylation and MLL Fusion Target Gene Expression.
(A) Upper panel: immunoblot analysis of H3K79me2 levels in MV4-11 (MLL-AF4), MOLM-13 (MLL-AF9), and Jurkat human leukemia cell lines following 4 days of treatment with EPZ004777 at indicated concentrations. Lower panel: time course of depletion of cellular H3K79me2 levels in MV4-11 cells treated with 3 μM EPZ004777.
(B) Immunoblot analysis of histones extracted from MV4-11 cells treated with 10 μM EPZ004777 with a panel of methyl-lysine and methyl-arginine residue specific antibodies.
(C) Quantitative real-time PCR analysis of HOXA9 and MEIS1 mRNA levels in MV4-11 and MOLM-13 cells following 6 day incubation with EPZ004777. Relative mRNA expression levels are plotted as a percentage of those in vehicle-treated control cells.
(D) Time course of HOXA9, MEIS1 and TBP mRNA expression in MV4-11 and MOLM-13 cells over 8 days of incubation with 3 μM EPZ004777 as measured by quantitative real-time PCR. Relative mRNA expression levels are plotted as a percentage of those at day 0. Error bars: standard deviation (SD).
