Molecular Pathogenesis of the Chronic Lymphocytic Leukemia, Regulation of the Cell Cycleand Apoptosis

Overview

In spite of the fact thatmany papers dealing with the chronic lymphocytic leukemia include a sentence in Introduction,that the molecular pathology of the disease „is still largely unknown“, the amount of accumulated information isimpressive and enables to create the first models of the overall genesis of this „most frequent leukemia in theWesternworld“. Sincemany studies have confirmed that B-CLL lymphocytes in peripheral blood are anchored in G0/G1-phaseof the cell cycle, the recent general opinion is, that CLL is primarily caused by defects in apoptosis – lymphocytesare slowly accumulating, being not able to „die properly“.However, it becomes evident, that in the microenvironmentappropriate for the cell growth, i.e. in the bone marrow and lymph nodes, B-CLL lymphocytes proliferate and theyare subsequently accumulated in peripheral blood. This review summarizes namely the knowledge about status andexpression of key genes regulating apoptosis and cell cycle in B-CLL lymphocytes, including p53, ATM, MDM2,Bcl-2/Bax, caspase-3, CDK-inhibitor p27, cyklins D2 and D3. Relationship between some of these genes and thestandard therapy is discussed and prospective therapeutic alternatives resulting from the newm olecular-geneticfindings are presented.

Key words:
chronic lymphocytic leukemia, cell cycle, apoptosis, therapy.