Fig. 3
Pharmacological inhibition of LSD1 enhances sensitivity to CFZ in B-cell malignancies. A U266PIR (20 nM CFZ; 0.5 µM SP2509), KMM-1PIR (10 nM CFZ; 0.5 µM SP2509), RPMI-8226PIR (60 nM CFZ; 1.5 µM SP2509), and AMO-1PIR (20 nM CFZ; 0.5 µM SP2509) cells were treated with SP2509, CFZ or the combination. Cell viability was measured by TMRM staining-flow cytometry 48-, 120-, 72-, and 96- hpt, respectively. B MM cell lines were treated with CFZ (1.25 nM for AMO-1, OPM2, LP1, U266; 2.5 nM for KMS-28, KMM-1; 5 nM for KMS-11, KMS-34, KMS-26, NCI-H929), SP2509 (0.1 µM for KMS-11, KMS-26, KMS-34; 0.25 µM for KMS-28; 0.5 µM for AMO-1, H929, U266, KMM-1, OPM2, LP1), or the combination. Cell viability was measured by TMRM staining-flow cytometry spanning a range between 24 and 120 hpt. C Sensitivity heatmap to DMSO, CFZ, SP2509, or the combination in a panel of B-cell lymphoma cell lines. Cells were treated with CFZ (1.25 nM for BL-41; 2 nM for U2932; 2.5 nM for Mino, SU-DHL-2, Daudi, Namalwa, Riva, Granta519; 3.75 nM for Karpas-422; 5 nM for Raji, HS-Sultan, DOHH-2, SU-DHL-7; 7.5 nM for OCI-Ly8), SP2509 (0.25 µM for Namalwa; 0.5 µM for Raji, HS-Sultan, Daudi, OCI-Ly8, Granta-519; 0.75 µM for Mino, Riva, Karpas-422; 1 µM for DOHH-2, BL-41, Su-DHL-7), or the combination. Cell viability was measured by TMRM staining-flow cytometry at 72 or 96 hpt. Heatmap was generated using RStudio and ggplot2 package. Data are the means ± s.d. of at least three independent experiments. Asterisks denote statistical significance (*P < .05; **P < .01; ***P < .001; ****P < .0001; ns > .05). hpt: hours post-treatment