Fig. 4: Prediction of essentiality of CTPS1 in MM with gmctool.

a Selected gMCS: {CTPS1, CTPS2} and gene expression in our cohort of patients, MMRF-CoMMpass and selected MM Cell Lines. b Boxplot of expression of the CTPS1 and CTPS2 genes in the B-cell differentiation (n = 5 for NB, n = 7 for CB, n = 7 for CC, n = 8 for MEM, n = 5 for TPC, n = 3 for BMPC, n = 33 for MM.non.responder and n = 4 for MM.responder), MMRF-CoMMpass (n = 223 for MM.non.responder and n = 544 for MM.responder) and MM Cell Lines (n = 1 for MM.non.responder and n = 7 for MM.responder). In the boxplots, the center line represents the median, the bounds of the box correspond to the 25th and 75th percentiles, the whiskers indicate the interquartile range by 1.5 times, and the circles are the outliers. c Correlation between the essentiality of CTPS1 (CRISPR knockout screen data, DepMap) and the expression of CTPS2 in log2(TPM + 1) (n = 851). Error bands denote the 95% confidence interval of the predicted values obtained from a linear regression model. Pearson correlation coefficient (ρ) and two-sided correlation test p-value are shown. d qPCR-RT of CTPS1 and CTPS2 expression in the selected cell lines. Data are referred to GUS gene. Data are presented as mean values of three experimental replicates. e Proliferation of CTPS1-deficient KMS-11, RPMI-8226 and KMS-12 cell lines obtained by CRISPR/Cas9 technology with three different sgRNAs. The proliferation percentage refers to cells infected with empty vector (Scramble, black line). Data represent mean ± standard deviation of three experimental replicates. f Proliferation of NCI-H929, KMS-11 and KMS-12 cell lines treated with CTPS1 inhibitor. The proliferation percentage refers to non-treated cells (black line). Data represent mean ± standard deviation of three experimental replicates. Note: ****/ns refer to the statistical significance level from an unpaired one-sided Wilcoxon test, respectively ****: p-value ≤ 0.0001 and ns: non-significant. Source data are provided as a Source Data file. BMPC bone marrow plasma cells, TPC tonsil plasma cells, MEM memory B cells, CC centrocytes, CB centroblasts, NB naïve B cells, MM.responder MM samples sensitive to CTPS1 inhibition, MM.non.responder MM samples resistant to CTPS1 inhibition.