P072 | Focal adhesion kinase FAK interplays with ROR1 in chronic lymphocytic leukemia

Introduction. Chronic lymphocytic leukemia (CLL) strongly depends on the tumor microenvironment, which supports cell survival, proliferation, and migration. Two key molecules emerge as crucial regulators in these processes: Focal Adhesion Kinase (FAK) and Receptor tyrosine kinase-like Orphan Receptor 1 (ROR1). FAK has been implicated in CLL progression, affecting the microenvironment dynamics. It interacts with molecules such as HS1 and cortactin, also involved in CLL pathogenesis. ROR1 shares connections with both these molecules and FAK pathways, suggesting a molecular network. This study investigates the potential interplay between FAK and ROR1 in CLL progression and aggressiveness.Methods. CD19+/CD5+ cells from therapy-free or ibrutinib-treated CLL patients were isolated by density gradient centrifugation. Flow cytometry and cell sorting were used to analyze FAK and ROR1 expression in different CLL subpopulations, the proliferating (CXCR4dim/CD5bright) and quiescent (CXCR4bright/CD5dim) ones. According to the experiments, leukemic cells were treated with 200nM Wnt5a, 200nM CXCL12, and 5μM defactinib, for the appropriate time. Cell migration was assessed using transwell assays, with migrated cells counted by flow cytometry. Protein expression and activation of FAK, ROR1, and HS1 were quantified by western blotting.Results. Our analysis found a significant correlation between FAK activation and ROR1 expression in CLL cells (r=0.41, p