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Review
. 2018 Mar 27;9(38):25332-25341.
doi: 10.18632/oncotarget.25011. eCollection 2018 May 18.

The B cell receptor signaling pathway in mantle cell lymphoma

Maria I Merolle  1 , Makhdum Ahmed  1 , Krystle Nomie  1 , Michael L Wang  1
Affiliations
Review

The B cell receptor signaling pathway in mantle cell lymphoma

Maria I Merolle et al. Oncotarget. .

Abstract

Signal transduction through the constitutively activated B cell receptor (BCR) plays a key role in the pathogenesis of B-cell tumors by promoting survival and proliferation of malignant B cells. The BCR signaling pathway is known to be deregulated in Mantle Cell Lymphoma (MCL) due to mutations or epigenetic events that impact regulatory proteins. One such protein is Bruton's tyrosine kinase (BTK), an integral component of the BCR signaling pathway. The success of ibrutinib, a BTK inhibitor, and other drugs that target components of the BCR pathway is evidence that regulation of the BCR signaling pathway is an effective method of MCL treatment. The complexity of the pathway indicates that it contains other potential therapeutic targets for the treatment of MCL. This is supported by recent and ongoing clinical trials of inhibitors of molecules such as PI3K, BCL-2, and BTK that show promising initial results. Additionally, agents that target different points of the pathway may have synergistic effects when used in combination. This review provides a description of the BCR signaling pathway on the molecular level followed by an explanation of its relationship to MCL. The role of the BCR signaling pathway in the pathogenesis of MCL is explained through an overview of the drugs that target BCR signaling in MCL treatment.

Keywords: B cell receptor; B cell signaling pathway; mantle cell lymphoma; targeted therapy.

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Conflict of interest statement

CONFLICTS OF INTEREST The authors have no conflicts to declare.

Figures

Figure 1
Figure 1. B-cell receptor signaling pathway
See this image and copyright information in PMC

References

    1. Woyach JA, Johnson AJ, Byrd JC. The B-cell receptor signaling pathway as a therapeutic target in CLL. Blood. 2012;120:1175–84. https://doi.org/10.1182/blood-2012-02-362624. - DOI - PMC - PubMed
    1. Rolli V, Gallwitz M, Wossning T, Flemming A, Schamel WWA, Zürn C, Reth M. Amplification of B cell antigen receptor signaling by a Syk/ITAM positive feedback loop. Mol Cell. 2002;10:1057–69. https://doi.org/10.1016/S1097-2765(02)00739-6. - DOI - PubMed
    1. Fearon DT, Carroll MC. Regulation of B lymphocyte responses to foreign and self-antigens by the CD19 CD21 complex. Annu Rev Immunol. 2000;18:393–422. https://doi.org/10.1146/annurev.immunol.18.1.393. - DOI - PubMed
    1. de Rie MA, Schumacher TN, van Schijndel GM, van Lier RW, Miedema F. Regulatory role of CD19 molecules in B-cell activation and differentiation. Cell Immunol. 1989;118:368–81. https://doi.org/10.1016/0008-8749(89)90385-7. - DOI - PubMed
    1. Liu C, Miller H, Hui KL, Grooman B, Bolland S, Upadhyaya A, Song W. A balance of Bruton's tyrosine kinase and SHIP activation regulates B cell receptor cluster formation by controlling actin remodeling. J Immunol. 2011;187:230–9. https://doi.org/10.4049/jimmunol.1100157. - DOI - PMC - PubMed

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