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. 2021 Sep 13;12:5395. doi: 10.1038/s41467-021-25403-y

Fig. 4. Biological processes operative in CLL with EMT-like networks.

Fig. 4

a–d Heatmap showing expression profiles (n = 337) for a genes indicating activated TNFα/NF-kB signaling, b EMT-TFs, c NOTCH target genes (intensity range −1:1), d histone lysine methyltransferases. FDRs of DEGs (GI vs. (I)EMT-L) are indicated on the right (q). CLL subtype color code defined in Fig. 4a applies for Fig. 4a–d, j–m. e GEP of the CD19 positive (+) and negative (−) compartment from CLL samples with inflammatory (I) and non-inflammatory (NI) signatures. f GEP of 2374 variably expressed genes for the CD19 negative fraction. g Tumor GEP indicating activated TNFα/NF-kB signaling and induction of EMT-like programs after BCL1 tumor transplantation. y-axis: median centered expression, x-axis: days (d) after transplantation of individual samples (p < 0.05 shown for d7 vs. d21, Mann–Whitney (two-sided)). h Heatmap showing gene set enrichment, characteristic for CLL with genomic instability or activation of EMT-like programs, in Eµ-Myc and Eµ-TCL1 mice. Gene sets were identified through GSEA (FDR < 0.05) on proteome profiles of splenic tumor cells from leukemic or terminal Eµ-Myc and Eµ-TCL1 mice (n = 4, in two pools) compared with B cells of tumor-free wild-type mice (n = 12, in two pools). Color-coded normalized enrichment scores (NES) (degree of enrichment; positive: yellow to red; negative: blue, light to dark). Gene sets are grouped according to the biological context. i Model illustrating biologic characteristics and regulatory interplay of processes in major subgroups (GI and (I)EMT-L), as specified in respective results sections. j Expression profiles for 2359 variably expressed genes (SD > 0.5). Genes with the highest significance (q < 1e−05) for the EMT-L, EBF1-r, and NRIP1 cluster are indicated. Fold change (FC) is indicated for EBF1-r specific genes (EBF1-r vs. all other). k Piecharts illustrating global gene expression, percentages indicating over- or under-expression in relation to the median expression per gene across the dataset. l Heatmap showing genes (n = 69) with strongest differential expression (q ≤ 0.05, FC ≥ 2) between the EBF1-r vs. all other clusters. CD19 sorted healthy donor B cells are included (orange). Arrowheads indicate cases with tri(12). m Agglomerative hierarchical clustering (2359 genes, Pearson complete) for n = 337 CLL and n = 5 healthy donor B cells (orange). For Fig. 4a–f, h–m, data within individual figures derives from biologically independent samples.