An overview of chronic lymphocytic leukaemia biology

Chronic lymphocytic leukaemia (CLL) is characterised by accumulation of CD5(+) monoclonal B cells in primary and secondary lymphoid tissues. Genetic defects and stimuli originating from the microenvironment concur to the selection and expansion of the malignant clone. Several lines of evidence, including molecular and functional analysis of the monoclonal immunoglobulin, support the hypothesis that stimulation through the B-cell receptor affects life and death of leukaemic cells. The microenvironment also has a critical role in the survival and accumulation of leukaemic cells within lymphoid organs where signals delivered from the surrounding cells are likely crucial in inducing proliferation. Nevertheless, several major biological issues still remain to be solved including regulation of the balance between proliferation and survival of leukaemic cells and the links between emerging gene abnormalities and microenvironment. In this context, mouse models are helpful tools in understanding disease mechanisms and in evaluating the efficacy of novel therapeutic agents.