Recent advances in the molecular biology and immunobiology of chronic lymphocytic leukemia

B-cell chronic lymphocytic leukemia (B-CLL) has long been viewed as a relatively homogeneous disease caused by the accumulation of monoclonal immature, immunoincompetent B cells with faulty apoptotic capacities. However, recent evidence, reviewed here, demonstrates that at least two different B-CLL subgroups exist with different clinical courses and outcomes. The malignant cells from both B-CLL subgroups are antigen-experienced cells that have a normal apoptotic apparatus and turnover continually. The leukemic cells of the two B-CLL subgroups have engaged antigen before transformation, although primarily the cells of patients in the poor outcome subgroup can respond to antigens following transformation. The difference in the ability to respond to antigen as a full-fledged B-CLL probably accounts for the different biological features and clinical outcomes of the patients in these subgroups.