Fig. 1. Venetoclax-sensitive MM exhibits reduced cellular energetics in contrast to the venetoclax-resistant cells.

a MM cell lines treated ±0.5 μM venetoclax (Ven) for 24 h were assessed for cell death by AnnexinV/4′,6-diamidino-2-phenylindole (DAPI) flow cytometric staining. Percent live normalized to vehicle control, with cell lines grouped by sensitivity. n = 3 independent experiments. Data are presented as mean values ± SEM. p value is calculated using a two-tailed Mann−Whitney test. b−d MM lines were evaluated for basal, coupled and maximal respiration in a mito stress assay using a Seahorse XF_e96 analyzer. n = 6 replicate Seahorse wells for each cell line except JJN3 (n = 11), U266 (n = 8) and KMS21BM (n = 7). OCR displayed are normalized to live cell number. Data are presented as mean values ± SEM. Venetoclax-sensitive MM exhibited significantly lower basal, maximal and coupled OCR (p values = 0.0022) determined after the addition of oligomycin, FCCP and antimycin/rotenone. p values are calculated using a two-tailed Mann−Whitney test. e Spare respiratory capacity in venetoclax-sensitive and -resistant cells was determined by subtracting basal OCR from maximal OCR. Data are presented as mean values ± SEM. Venetoclax-resistant lines have been shown in green and venetoclax-sensitive lines have been shown in purple bars in (a−e). f Heat map of electron transport chain-specific gene expression in t(11;14) vs. non-t(11;14) patients derived from the CoMMpass trial RNAseq. Statistical significance (adjusted p value < 0.01) is highlighted for gene names in bold-italic font. Source data are provided as a source data file.