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Fig. 6 | Clinical Epigenetics

Fig. 6

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

Fig. 6

UNC-0379 treatment sensitizes HMCLs to Melphalan-induced DNA damage. a Dose–response matrix inhibition and landscape representation for experimentally measured drug synergy in XG7 cells treated with increased concentration of the combination of melphalan and SETD8 inhibitor (UNC-0379). Synergy scores are displayed using a continuous pseudo-color scale ranging from dark-green = antagonistic to dark-red = synergistic b Landscape and 3-D matrix representation for experimentally measured drug synergy in XG1 cells. c Number of 53BP1 foci in XG7 and XG1 HMCLs, treated with melphalan (3 µM), UNC-0379 (3 µM) or the combination of the two drugs for 6 h or 24 h as indicated. Number of foci per cell was quantified using ImageJ software (mean number of cells counted: 300). Statistical significance between conditions was assessed using Student paired t test (*p value < 0.05). d Measure of 53BP1 foci in melphalan-resistant XG7 cells treated with melphalan (15 µM), UNC-0379 (3 µM) or the combination of the two drugs for 24 h. Number of foci per cell was quantified using ImageJ software (mean number of cells counted: 300). Statistical significance between conditions was assessed using Student paired t test (*p value < 0.05). e Measure of AnnexinV-positive cells in the same drug concentrations as in D. AnnexinV-PE staining was analyzed by flow cytometry 96 h after drug treatment. Statistical significance between conditions was assessed using Student paired t test (*p value < 0.05)

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