Fig. 2.

Treatment of NOTCH1-mutated MCL cells with OMP-52M51 effectively prevents DLL4-dependent activation of Notch1. a Mino and JeKo-1 MCL cells and NOTCH1-mutated primary MCL cells (patient sample MCL) were treated with OMP-52M51 or IgG2 control antibody and stimulated with human recombinant DLL4 (4 μg/mL). Protein expression of cleaved Notch1 was determined by Western Blot analysis after 24 and 48 h. b Mino and JeKo-1 MCL cells were treated with OMP-52M51 and cocultured with DLL4-overexpressing OP9-stromal cells or GFP-transfected control cells. After 48 h, Western Blot analysis of cleaved Notch1 protein expression was performed. c Significantly modulated genes (FDR < 0.123; p < 0.005; NES > 1.48) related to the Notch1 signaling pathway (NOTCH custom) upon stimulation of Mino and JeKo-1 cells with DLL4 after 48 h obtained with the Gene Set Enrichment Analysis (GSEA) software. d Significantly upregulated genes (FDR < 0.001; p < 0.001, NES = 3.00) upon stimulation of Mino and JeKo-1 cells with DLL4 after 48 h obtained with GSEA applying a signature of Notch target genes described in MCL cells (NOTCH direct targets). Heatmaps were hierarchical clustered by one minus Pearson correlation of the average of gene expression