Deciphering the functional interactome of extracellular vesicle-derived B cell receptor-associated kinases in the chronic lymphocytic leukemia microenvironment

Chronic Lymphocytic Leukemia (CLL), the most prevalent leukemia in the elderly, is characterized by heterogeneity in progression and treatment responses. Recent advances, such as the introduction of tyrosine kinase inhibitors, have transformed the therapeutic landscape by targeting the B cell receptor (BCR) signaling pathway, fundamental for CLL progression. Central to this pathway are BCR-associated kinases (BAKs) like LYN, SYK, and BTK, expressed both in malignant B cells, the tumor microenvironment (TME) and extracellular vesicles. Given the crucial role of the complex TME in influencing CLL behavior, recent attention has highlighted extracellular vesicles (EVs) released by leukemic cells as key players in shaping the TME.

Our project utilizes novel methodologies, such as BioID2 proximity-dependent biotin identification technique and mass spectrometry, mass cytometry, and imaging mass cytometry, to uncover the functional interactome of EV-derived BAKs within the CLL TME. Two primary aims underpin this project: first, to elucidate the interactome of BAKs in distinct TME cell types, and second, to investigate the EV-dependent interactome of these kinases.

By deciphering the intricate interplay of BAKs, EVs, and the TME, our research aims to illuminate novel pathways and interaction partners that could revolutionize CLL therapeutic strategies, targeting both CLL cells and their supportive microenvironment. The findings hold the potential to enhance our understanding of CLL's TME dynamics, leading to innovative TME-based treatment approaches for this prevalent form of leukemia.

Labor für molekulare Pathogenese der CLL - Arbeitsgruppen & Labore - Forschung | Onkologie Uniklinik Köln (