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Fig. 2 | Clinical Epigenetics

Fig. 2

From: Targeting the methyltransferase SETD8 impairs tumor cell survival and overcomes drug resistance independently of p53 status in multiple myeloma

Fig. 2

SETD8 inhibitor UNC-0379 is highly toxic to malignant plasma cells. a Graphical representation of HMCLs viability upon exposure to various concentrations of UNC-0379. Color scale represents cell viability, from the highest (blue) to the lowest (red) values. The IC50 value of each tested HMCL is indicated. Data are mean values ± standard deviation (SD) of five experiments determined on sextuplet culture wells. b The first bar graph results from the quantitation of cell cycle distribution of control (untreated) and UNC-0379-treated XG7 and XG25 HMCLs 48 h after treatment. After short-pulse of BrdU incorporation, cell cycle was analyzed by FACS using DAPI and anti-BrdU antibody. Second bar graph represents the results from the quantitation of apoptosis in control and UNC-0379-treated XG7 and XG25 HMCLs by flow cytometry with AnnexinV-PE staining at 96 h after UNC-0379 treatment. Data shown are mean values ± SD of 4 separate experiments. Statistical analysis was done with a paired t test. (*) indicates a significant difference compared to control cells using a Wilcoxon test for pairs (p ≤ 0.05). c Percentage of normal mature plasma cells (CD38 + CD138 +) from two different donors and quantified by FACS after in vitro treatment with increasing concentrations of UNC-0379 or the vehicle DMSO at the highest concentration (MOCK) for 4 days. Samples were treated and analyzed in duplicates. d Percentage of in vitro cultivated primary MM cells (CD138 + tumor cells) and bone marrow microenvironment (CD138- non-malignant cells) upon increasing concentrations of UNC-0379 treatment for 4 days. Data shown are mean values of 8 patient samples. *Indicates a significant difference compared to control cells using a Wilcoxon test for pairs (p ≤ 0.05)

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