Fig. 2: Ibrutinib resistance is not driven by genetic mutations but likely related to post-translational modifications. | Nature Communications

Fig. 2: Ibrutinib resistance is not driven by genetic mutations but likely related to post-translational modifications.

From: Longitudinal omics data and preclinical treatment suggest the proteasome inhibitor carfilzomib as therapy for ibrutinib-resistant CLL

Fig. 2: Ibrutinib resistance is not driven by genetic mutations but likely related to post-translational modifications.

A Experimental design and treatment schedule of in vivo assay and overview of WES, RNA-sequencing and proteomic approaches on FACS-sorted murine CLL splenocytes. Created in BioRender. Zapatka, M. (2025) https://BioRender.com/a06v191. B RNA-sequencing of FACS-sorted murine CLL splenocytes. Unsupervised hierarchical clustering of the most variable transcripts comparing Ibr resistance (I-late, n = 3) vs Ibr sensitive (I-early, n = 4), and vehicle groups (V-late, n = 4 and V-early, n = 4) using LIMMA tool. C Over-representation analysis of significantly deregulated (FDR < 0.05) ibrutinib-resistant-specific transcripts showing enriched terms. D Venn diagram showing the overlap between robustly detected transcripts and identified proteins. E Heatmap visualization of matched pairs between transcripts found either significantly up- (up) or down-regulated (down) in ibrutinib-resistant samples and the respective proteins, and ranked by abundance in the ibrutinib-resistant proteome. F Over-representation analysis of transcripts up-regulated in ibrutinib-resistant mice and showing normalized protein abundance in log 2 higher than 0.5 (red) or lower than −0.5 (blue). Source data are provided as a Source Data file Fig. 2.

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