Figure 4.

(a) Human MM cell lines display differential and dose-dependent sensitivities to 5-AZA. Single-agent dose–response curves were constructed in human MM cell lines (JJN3 and U266) treated with 5-AZA for 24 and 48 h. (b) Synergistic induction of apoptosis in JJN3 and U266 cells with panobinostat was combined with 5-AZA after 48 h (CI<0.9) *P<0.05 verses single agents: (c) JJN3 cells or (d) U266 cells were treated with panobinostat, 5-AZA or the combination of both agents at synergistic concentrations (described in Figure 4b) and assessed for changes in gene expression using next-generation RNA sequencing after 24 h. Gene set enrichment was assessed using CAMERA.⁴⁰ Each Venn diagram depicts the number of MSigDB gene sets enriched within each treatment and within each cell line (two-sided P<0.05, n=3); (e) demonstrates the number of distinct or overlapping MSigDB gene sets enriched when JJN3 or U266 cells were treated with the combination of panobinostat with 5-AZA