Last update:
08-Apr-2008

B-chronic lymphocytic leukemia (CLL) is the most common type of leukemia in western countries. Research during the last two decades has contributed to better understanding of the biology of the disease. Two subtypes of CLL have been identified, according to the presence or absence of somatic hypermutations of the variable region of the immunoglobulin (IgV) gene. The differences cover the entire course of the disease, including the cellular origin and behavior and the pathophysiology. The most striking difference between the two subtypes is the poorer prognosis of the unmutated form. CLL is a clinically heterogeneous disease with a survival estimate ranging from months to many years. Its heterogeneity reflects the diversity of pathogenic mechanisms that act upon the B-memory cell, including the antigenic stimulation of B-cells, chromosomal abnormalities and gene mutations, and down-regulation of the apoptotic pathways due to survival signals from the tissue microenvironment. No accurate prognosis can be made for patients in the first stages of disease, which creates the need for prognostic markers that enable timely identification of aggressive forms. Apart from the detection of IgV mutations, a procedure that cannot be performed in many peripheral health centers, testing for zeta-associated protein of 70 kDa (ZAP-70) is highly recommended. CLL B-cells, especially those of the unmutated type, express high levels of ZAP-70, indicative of aggressive disease and shorter survival. ZAP-70 testing, combined with other prognostic factors, is expected to play a central role in patient management. Current clinical trials are evaluating chemotherapeutic combination regimens and are also testing the feasibility of bone marrow transplantation, in the hope of accomplishing cure.

Key words: Biology, Chronic lymphocytic leukemia, Pathogenesis, Prognostic factors, Treatment options.