Review Article | Published:

Targeting pathological B cell receptor signalling in lymphoid malignancies

Nature Reviews Drug Discovery volume 12, pages 229243 (2013) | Download Citation

Abstract

Signalling through the B cell receptor (BCR) is central to the development and maintenance of B cells. In light of the numerous proliferative and survival pathways activated downstream of the BCR, it comes as no surprise that malignant B cells would co-opt this receptor to promote their own growth and survival. However, direct evidence for BCR signalling in human lymphoma has only come to light recently. Roles for antigen-dependent and antigen-independent, or tonic, BCR signalling have now been described for several different lymphoma subtypes. Furthermore, correlative data implicate antigen-dependent BCR signalling in many other forms of lymphoma. A host of therapeutic agents targeting effectors of the BCR signalling pathway are now in clinical trials and have shown initial success against multiple forms of lymphoma.

Key points

  • B cell receptor (BCR) signalling is central to the development, maintenance and activation of normal B cells.

  • Malignant B cells co-opt the numerous proliferative and survival pathways activated downstream of the BCR to promote their own growth and survival.

  • Antigen-dependent and antigen-independent, or tonic, BCR signalling have recently been implicated in different lymphoma subtypes.

  • Many therapeutic agents targeting effectors of the BCR signalling pathway are now in clinical trials to evaluate their efficacy against B cell lymphomas.

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Acknowledgements

This research was supported by the Intramural Research Program of the US National Institutes of Health, National Cancer Institute, Center for Cancer Research.

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  1. Metabolism Branch, Center for Cancer Research, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland 20892, USA.

    • Ryan M. Young
    •  & Louis M. Staudt

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