Role of BAFF and APRIL in human B‐cell chronic lymphocytic leukaemia

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Abstract
Summary: B‐cell chronic lymphocytic leukaemia (B‐CLL) is the most prevalent leukaemia in Western countries and is characterized by the gradual accumulation in patients of small mature B cells. Since the vast majority of tumoral cells are quiescent, the accumulation mostly results from deficient apoptosis rather than from acute proliferation. Although the phenomenon is relevant in vivo, B‐CLL cells die rapidly in vitro as a consequence of apoptosis, suggesting a lack of essential growth factors in the culture medium. Indeed, the rate of B‐CLL cell death in vitro is modulated by different cytokines, some favouring the apoptotic process, others counteracting it. Two related members of the tumour necrosis factor family, BAFF (B‐cell activating factor of the TNF family) and APRIL (a proliferation‐inducing ligand), already known for their crucial role in normal B‐cell survival, differentiation and apoptosis, were recently shown to be expressed by B‐CLL cells. These molecules are able to protect the leukaemic cells against spontaneous and drug‐induced apoptosis via autocrine and/or paracrine pathways. This review will focus on the role of BAFF and APRIL in the survival of tumoral cells. It will discuss the expression of these molecules by B‐CLL cells, their regulation, transduction pathways and their effects on leukaemic cells. The design of reagents able to counteract the effects of these molecules seems to be a new promising therapeutic approach for B‐CLL and is already currently developed in the treatment of autoimmune diseases.