Proteins involved in the DNA repair and the cell cycle pathways are common interaction partners of TCL1A. (A) Experimental setup: TCL1A coimmunoprecipitations (co-IPs) were performed from lysates of primary CLL cells, divided into 2 subgroups based on their IGHV gene mutation status. Primary B cells isolated from tonsils were used as healthy controls (N = 3). Co-IPs with immunoglobulin G (IgG) served as a negative control (N = 3, CLL lysates). Processed immunoprecipitates were analyzed on a label-free quantification (LFQ) LC-MS/MS device. (B) Venn diagrams showing the overlap of identified TCL1A-interacting proteins between healthy B cells from tonsils and CLL cells, as well as between U-CLL and M-CLL (for the comparison of cytogenetic/clinical-risk groups “no go” vs “slow go” vs “high-risk,” see supplemental Figure 3). Proteins were considered interactors when they were significantly enriched in the corresponding group vs IgG control (FDR q < 0.05, FCh >2, Welsh test). (C) Overview of enriched pathway clusters within the TCL1A interactome identified by overrepresentation analysis (ORA) using the Cytoscape plug-in ClueGO (version 2.5.8, Reactome database), indicating the percentage of terms per cluster. Supplemental Figure 4 shows the associated functional networks of all enriched pathways identified by ClueGO. (D) Bar graph of selected pathways identified in panel C illustrating the percentage of associated proteins from the TCL1A interactome within each pathway. Heat map of TCL1A interactors belonging to the cell cycle pathway (E) and the DNA repair pathway (F) as identified by ORA using ClueGO. BCR, B-cell receptor; HCMV, human cytomegalovirus; mRNA, messenger RNA; SARS-CoV, severe acute respiratory syndrome coronavirus.