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

Immunology. 2006 Jul;118(3):281-92. doi: 10.1111/j.1365-2567.2006.02377.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • B-Cell Activating Factor
  • Biomarkers, Tumor / blood
  • Cell Survival
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / blood*
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Membrane Proteins / blood
  • Membrane Proteins / physiology*
  • Neoplasm Proteins / blood
  • Neoplasm Proteins / physiology
  • Tumor Necrosis Factor Ligand Superfamily Member 13
  • Tumor Necrosis Factor-alpha / physiology*


  • B-Cell Activating Factor
  • Biomarkers, Tumor
  • Membrane Proteins
  • Neoplasm Proteins
  • TNFSF13 protein, human
  • TNFSF13B protein, human
  • Tumor Necrosis Factor Ligand Superfamily Member 13
  • Tumor Necrosis Factor-alpha