Fig. 3 | Scientific Reports

Fig. 3

From: SAMHD1 dysfunction impairs DNA damage response and increases sensitivity to PARP inhibition in chronic lymphocytic leukemia

Fig. 3

Response of SAMHD1KO cells to olaparib in monotherapy and combined with bendamustine/ ibrutinib. (A) Cell viability studies by MTT assay in response to increasing doses of olaparib (0.625–20 µM) for 72 h. Percentage of live cells is expressed relative to DMSO control. Differences between PGA-1 SAMHD1WT and SAMHD1KO clones are summarized by asterisks. Data are summarized as the mean ± SD of three independent experiments. (B) Drug response to olaparib (20 µM), bendamustine (20 µM) and combination of both drugs (ratio 1:1) in PGA-1 SAMHD1WT and SAMHD1KO by measuring cell viability with MTT assay after 72 h Data are summarized as the mean ± SD of three independent experiments. (C) Dose–response curve of viable cells (%, relativized to untreated cells) after treatment with olaparib, ibrutinib and their combination at a 1:1 ratio. Data are presented as the mean ± SD of three independent experiments. Combination index (CI) was calculated using Calcusyn. (D) Determination of cytotoxicity after 48-h treatment with olaparib (7.5 µM), ibrutinib (7.5 µM) and the combination of these drugs (1:1) in PGA-1 cells by measuring the percentage of apoptotic cells (annexin V + / PI +) with annexin V/PI staining. Data are presented as the mean ± SD of three independent experiments. (E) Western blot analyses reflecting PARP cleavage as an apoptosis marker after treatment with olaparib, ibrutinib and their combination (ratio 1:1).

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