IGpath · Dissecting the functional pathways of B cell receptor immunoglobulin in antigen driven mature B cell lymphomas

Dissecting the functional pathways of B cell receptor immunoglobulin in antigen driven mature B cell lymphomas

Chronic lymphocytic leukemia (CLL) is a mature B cell lymphoma (B-NHL), the most common adult hematologic malignancy. Splenic marginal zone lymphoma (SMZL) is an indolent B-NHL characterized by massive splenomegaly and moderate lymphocytosis. Both CLL and SMZL affect the elderly population (median age at diagnosis >70 years). About two-thirds of CLL patients and one-half of SMZL patients will eventually require treatment at any stage of their disease. However, despite the therapeutic progress achieved in recent years, both entities remain currently incurable. The cause and the exact pathogenesis mechanisms of the distinct types of B-NHLs remains unknown. However, accumulating evidence supports that the B cell receptor immunoglobulin (BcR IG) holds a pivotal role in B-NHL ontogeny mediating critical interactions with the microenvironment, including binding to antigen and B cell activation by initiating an intracellular signaling cascade. The clinical relevance of BcR IG-mediated signaling is highlighted by the efficiency of BcR signaling inhibitors in B-NHL management. Nevertheless, open issues abound regarding the precise role of the BcR IG in lymphomagenesis, particularly regarding the nature and the range of the antigenic interactions and the functional consequences on the (pre)malignant clones and the clinical outcome. To complicate things further, in CLL a novel type of BcR signaling has been reported, namely BcR autonomous signaling, that is independent of external antigen triggering and lays on the ability of CLL BcR IG to self-associate. The overall objective of IGpath was to dissect the BcR IG-related processes implicated in the pathogenesis of CLL and SMZL. Furthermore, to refine our understanding of the early stages of lymphomagenesis we investigated these mechanisms also in BcR IG from individuals with monoclonal B lymphocytosis (MBL), a pre-malignant condition that is considered as a potential precursor state to CLL. The refinement of the IG BcR-related mechanisms of pathogenesis may have implications for the clinical management since it can assist in the ‘functional’ classification of patients (or people at high-risk of developing overt disease) based on the type of antigenic stimulation, a step towards personalized medicine.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз