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. Author manuscript; available in PMC: 2015 Dec 1.
Published in final edited form as: Mol Cancer Ther. 2014 Sep 19;13(12):2886–2897. doi: 10.1158/1535-7163.MCT-14-0220

Figure 1. ACY1215 interacts synergistically with CFZ in multiple NHL models and primary DLBCL cells, but not in normal cells.

Figure 1

(A–B) Cells were treated with minimally toxic concentrations of CFZ (SUDHL16-2.5 nM, SUDHL4, U2932 and Granta 519-3.5 nM, Rec-1–15 nM, OCI-LY18-3.0 nM) in the presence or absence of ACY1215 (1.5–2.0 µM) for 48h, after which cell death was monitored by 7-AAD staining and flow cytometry (C) Fractional Effect (FA) values were determined by comparing results obtained for untreated controls and treated SUDHL16 cells following exposure to agents (36h) administered at a fixed ratio (CFZ:ACY1215::2.5:1500), as per Median Dose Effect analysis. Combination Index (C.I.) values less than 1.0 denote a synergistic interaction. (D) SUDHL16 cells were treated with varying CFZ (1.5–3.5 nM) concentrations in the presence or absence of fixed concentrations of ACY1215 (1.5–2.0 µM); alternatively, (E) cells were treated with varying ACY1215 (0.5–2.0 µM) concentrations ± fixed concentrations of CFZ (2.0–2.5 nM) for 48h, after which cell death was monitored by flow cytometry and AnnexinV/PI staining. (F) Primary human DLBCL (ABC subtype) mononuclear cells (90% purity) were isolated as described in Methods and resuspended in medium containing 10% FCS at a density of 0.6 × 106 cells/mL. Bone marrow CD34+ cells were isolated as described in Methods. Both samples were exposed to CFZ (10 nM) ± ACY1215 (1.25 µM) for 14h. Cell death was monitored by Annexin V/PI staining. For all studies, values represent the means for 3 independent experiments performed in triplicate ± S.D. For A–B * = significantly more than values obtained for CFZ or ACY1215 treatment alone; P < 0.02. D–F, * = significantly greater than values obtained for CFZ or ACY1215 treatment alone P < 0.04.