Cytotoxic effect of BET inhibition in malignant B-cell lines and CLL patient-derived B cells is independent of survival signals. Cytotoxic effect of BET.

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Cytotoxic effect of BET inhibition in malignant B-cell lines and CLL patient-derived B cells is independent of survival signals. Cytotoxic effect of BET inhibition in malignant B-cell lines and CLL patient-derived B cells is independent of survival signals. A and B, Dose-dependent decrease of proliferation of CpG-stimulated primary CLL cells upon BRD4 inhibition with increasing doses of PLX51107, OTX015, JQ1, or iBET762 for 72 hours continuously (A) or for 4 hours followed by washout (B). Symbols represent individual patient data, black lines represent averages. C, CD19-positive cells from patients with CLL (n = 13) were cocultured with human Hs27 or murine 9-15c bone marrow–derived stroma and incubated with PLX51107 (1, 2, or 5 μmol/L) for 72 hours, after which CLL cell viability was determined by Annexin V/PI staining. Red lines represent averages. D, Dose-dependent decrease of proliferation of MEC-1 and OCI-LY1 treated with increasing doses of PLX51107, OTX015, JQ1, or iBET762 for 72 hours (n = 3 independent experiments per cell line). P < 0.001 for all inhibitors and each cell line. Hatice Gulcin Ozer et al. Cancer Discov 2018;8:458-477 ©2018 by American Association for Cancer Research