Onkológia 2/2014

Pathogenesis of chronic lymphocytic leukemia

Chronic lymphocytic leukemia is the most common leukemia in adults. Recognition that B-cell receptor (BCR) signaling is essential for the proliferation and survival of chronic lymphocytic leukemia cells stands as one of the important insights into the pathobiology of the disease. Antigen-dependent and – independent BCR signaling plays a central role in the pathogenesis of CLL. There were developed a lot of kinases – enzymes responsible for signal transmision. Well-characterized molecular markers correlate with adverse prognosis, such as unmutated immunoglobulin heavy-chain chains and ZAP70 expression, are now associated with BCR-signaling activity. The conventional view of CLL had been that it is a disease of failed apoptosis and CLL cells are passively accumulated. Recent observations suggest that CLL cells have significant proliferative capacity, they proliferate in the proliferation centers or pseudofollicles. CLL cells need signals and interactions from the microenvironment of lymphatic tissue for survival and expansion. These new information improve understanding of disease pathogenesis and facilitate the development of novel therapeutic strategies.

Keywords: chronic lymphocytic leukemia, pathogenesis, B cell receptor.