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. Author manuscript; available in PMC: 2022 Jun 1.
Published in final edited form as: Clin Cancer Res. 2021 Sep 13;27(23):6432–6444. doi: 10.1158/1078-0432.CCR-21-2040

Figure 5. Selective metabolic dependencies induce susceptibility to pharmacologic inhibitors of OxPhos in re-programmed myeloma cells.

Figure 5.

A. Kinetics of metabolic flux in untreated (naiïve) and persistent U266 myeloma cells (single-cell clone C). OCR/ECAR ratio is significantly higher in persistent cells at baseline and after adding FCCP to stimulate maximal mitochondrial capacity. B. Oxygen consumption rate (OCR, pmol/min) over extracellular acidification rate (ECAR, mpH/min) in persistent versus naïve U266 cells shown at baseline for U266 clone C. Disproportionally greater decline of ECAR compared to OCR levels in persistent cells. C. OCR/ECAR ratio in naïve and persistent U266 cells (clone C, baseline consumption, n=5, P<0.0001) D. Viability of U266 cells after treatment with dabrafenib (day 1–14) and subsequent rotenone titration (day 15–21). Pretreatment with dabrafenib significantly increases sensitivity to rotenone in U266 (P=0.02, clone C) as compared to DMSO control. E. In vivo assessment of metabolic reprogramming by examination of OxPhos-related genes in normal and malignant single plasma cells from patients with BRAF-mutated myeloma by single-cell RNA-seq. Heatmaps and GSEA plots show differentially expressed genes derived from the KEGG oxidative phosphorylation gene set (hsa00190) in treated vs. untreated primary cells (P<0.05 in ≥1 patient).