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Nat Rev Immunol. 2013 Aug;13(8):578-91. doi: 10.1038/nri3487.

New insights into pre-BCR and BCR signalling with relevance to B cell malignancies.

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Program on Inflammatory Diseases, Infectious and Inflammatory Diseases Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA.

Erratum in

  • Nat Rev Immunol. 2013 Sep;13(9):701.


The B cell receptor (BCR) and its precursor (pre-BCR) control B cell homeostasis, differentiation and function. Moreover, aberrant pre-BCR and BCR signalling have a central role in B cell neoplasia; for example, enhanced positive signalling or disrupted negative signalling downstream of the pre-BCR promotes B cell acute lymphocytic leukaemia. The emerging distinctions between tonic and chronic active BCR signalling have contributed to the identification of oncogenic targets downstream of BCR signalling in mature B cell neoplasms. Indeed, the encouraging results of several ongoing clinical trials that target the activity of phosphoinositide 3-kinase δ-isoform (PI3Kδ), Bruton tyrosine kinase (BTK) or spleen tyrosine kinase (SYK) downstream of the BCR highlight the therapeutic potential of inhibiting BCR signalling.

[Indexed for MEDLINE]

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