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Targeting pathological B cell receptor signalling in lymphoid malignancies

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.

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.

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Figure 1: B cell receptor signalling basics.
Figure 2: Two forms of pathological B cell receptor signalling in lymphoid malignancies.

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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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Young, R., Staudt, L. Targeting pathological B cell receptor signalling in lymphoid malignancies. Nat Rev Drug Discov 12, 229–243 (2013). https://doi.org/10.1038/nrd3937

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