Role of BAFF and APRIL in human B-cell chronic lymphocytic leukaemia.
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.
Haiat
Stéphanie
S
UMRS INSERM 736/University Paris 6, Centre de Recherches Biomédicales des Cordeliers, Paris, France.
Billard
Christian
C
Quiney
Claire
C
Ajchenbaum-Cymbalista
Florence
F
Kolb
Jean-Pierre
JP
D053264:B-Cell Activating Factor; D014408:Biomarkers, Tumor / Q000097:blood; D002470:Cell Survival; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000473:pathology; D008565:Membrane Proteins / Q000097:blood / Q000502:physiology*; D009363:Neoplasm Proteins / Q000097:blood / Q000502:physiology; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D053264:B-Cell Activating Factor; D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C114631:TNFSF13 protein, human; C505719:TNFSF13B protein, human; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D014409:Tumor Necrosis Factor-alpha