Treatment with EZH2i/HDACi/DNMTi reactivated CTBP2 and suppressed MYC expression in primary MM cells. The CD138+ cells isolated from patients with MM (n = 7) were treated with EPZ-6438 (EPZ) at 5 μM, Panobinostat (Pano) at 5 nM, alone or in combination (E+P), and 5-Aza-2’-deoxycytidine (5-Aza-dC) at 10 μM for 48 hours. Dimethyl sulfoxide was used as a control treatment. Effect of epigenetic agents on primary MM samples on (A) cell growth as measured by the CellTiter-Glo assay, and mRNA expression of (B) CTBP2 and (C) MYC was detected by RQ-PCR with GAPDH as a loading control. (D-E) Patients were equally categorized into the CTBP2^low and CTBP2^high groups based on their baseline CTBP2 expression. The effects of dual EZH2i/HDACi treatment between the 2 groups were compared for their (D) sensitivity to drug treatment as measured by the CellTiter-Glo assay, and (E) expression of CTBP2 as detected by RQ-PCR with GAPDH as a loading control. In panels A-C, the error bars represent the SD of the 3 technical replicates. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001, ∗∗∗∗P < .0001. DMSO, dimethyl sulfoxide.