Fig. 5
From: Bortezomib resistance in multiple myeloma is associated with increased serine synthesis
Bortezomib resistance correlates to the expression of PHGDH. a Graphical representation of quantitative proteomics data. Proteins are ranked in volcano plot according to their statistically p-value (y-axis) and relative abundance ratio between RPMI-8226 wild type (WT) and bortezomib resistant (BTZ/100 cells) (x-axis). Colored spots represent significantly upregulated (red) or downregulated (green) proteins in BTZ/100 cells with at least a 5-fold change. Significantly regulated metabolic enzymes are marked. b Quantitative proteomics data of enzymes involved in the serine synthesis pathway. Data represents means ± SD (n = 3). c Immunoblot of 3-phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1), phosphoserine phosphatase (PSPH) and Tubulin expression in RPMI-8226, AMO-1 and ARH-77 bortezomib-sensitive and -resistant cells. d Fractions of serine M+3 in RPMI-8226, AMO-1 and ARH-77 bortezomib-sensitive and -resistant cells. Data represent % serine M+3 of total serine ± SD (n = 3). One-way ANOVA tests were performed (**** = p < 0.0001). e Correlation between serine M+3 fractions and bortezomib sensitivity in RPMI-8226, AMO-1 and ARH-77 bortezomib-sensitive and -resistant cells. IC50s were determined in cell viability assay after 48 h of increasing concentrations of bortezomib. Pearson correlation r = 0.56 (p = .0042). f Immunoblot of PHGDH, PSAT1 and PSPH in isolated CD138+ plasma cells from diagnosed multiple myeloma patients (n = 6). Patients with progressive disease/refractory to BTZ-containing therapy are indicated with *. PHGDH is blotted on a separate membrane. BTZ = bortezomib, CFZ = carfilzomib, PHGDH = 3-phosphoglycerate dehydrogenase, PSAT1 = phosphoserine aminotransferase 1, PSPH = phosphoserine phosphatase, SSP = serine synthesis pathway