Biological and Clinical Heterogeneity of B-cell Chronic Lymphocytic Leukemia

B-cell chronic lymphoproliferative disorders have been recognized as a heterogeneous group of neoplastic diseases affecting the lymphoid system. They are frequently characterized by leukemic manifestations with peripheral blood and/or bone marrow involvement. B-cell chronic lymphocytic leukemia (B-CLL), a disease which is now accepted as derived from immunologicallycompetent antigen-activated B-cells, is the most common in the western countries. Although for several decades it was considered as a unique entity, a body of evidences is now emerging indicating the biological heterogeneity of B-CLL. Molecular and immunophenotypic data induce to consider two main subgroups of B-CLL exist at the cellular level: in fact, B-CLL cases can be divided into two categories according to IgV gene mutation status. One group develops from "memory" B-cells after antigenic stimulation in the germinal center of secondary follicles, displays mutated gene IgV and lacks CD38 expression; the second one derives from the so-called "naïve" antigen inexperienced B-cells, does not present IgV gene mutations and displays CD38 surface molecule. The two groups seem to be characterised by different clinical outcomes with the "mutated" group expected to have a more benign course than that arising from a "naïve" B-cell. Thus, the definition of the biological features of these different groups could be of help for clinicians in order to recognize patients needing more intensive therapeutic approaches.