Fig. 1

CircFBXW7 is depleted in T-ALL patients and its silencing has functional impact in T-ALL in vitro. A The boxplot shows the normalized expression of circFBXW7 in 110 patients with T-ALL of two cohorts (TALL_1 and TALL_2, 25 and 85 cases at diagnosis) and in the normal immature T-cell counterpart, represented by sorted human thymocyte populations CD34⁺ (CD34⁺CD4⁻CD1⁻, CD34⁺CD4⁻CD1⁺, CD34⁺CD4⁺) and DP (CD4⁺CD8⁺CD3⁻ and CD4⁺CD8⁺CD3⁺) from healthy donors; the gray density plots indicate the distribution of values across the ranges. B Real-time PCR quantification of circFBXW7 and FBXW7 mRNA in RPMI-8402 cell lines at 48 h after transfection in RPMI-8402 cells (Relative expression provided by ΔCt values using GAPDH as calibrator). C Cell viability upon circFBXW7 silencing, evaluated by MTT assay at 24, 48 and 72 h post transfection in RPMI-8402 cells. D Cell proliferation upon circFBXW7 silencing, evaluated by EdU assay at 24, 48 and 72 h post transfection in RPMI-8402 cells (mean ± SE from 3 independent experiments. **p < 0.01, ***p < 0.001). E Dot-plot of the activity of top GO terms significantly activated according to microarray gene expression profiling upon circFBXW7 silencing at 48 h, plotted in order of gene ratio. The size and the color of the dots represent respectively the number of genes associated with the significantly enriched GO term, and the adjusted p-value (BH) of the enrichment. F Multidimensional Scaling (MDS) plot based on Best-Match Average distance, representing the proximities of enriched GO term clusters. The dot size depends on the number of GO terms within each cluster. G Heatmap MSigDB Hallmark gene sets variation score and score difference in RPMI-8402 cells at 48 h after circFBXW7 silencing according to GSVA analysis. H Volcano plot of DEGs between high- and low-circFBXW7 expression groups in RPMI-8402. Labels show MYC targets and NOTCH signaling genes deregulated. I Western blot quantification of MYC and cleaved active intracellular NOTCH1 after circFBXW7 silencing and in control RPMI-8402 cells. J Schematic model of circFBXW7 relations with FBXW7, MYC, and NOTCH1 (red and green arrows indicate up and downregulation). K Connectivity score between the gene expression perturbation upon circFBXW7 silencing and drug LINCS signatures (positive and negative values are indicated in red and blue, respectively)