Oncotarget

Reviews:

The B cell receptor signaling pathway in mantle cell lymphoma

Maria I. Merolle _, Makhdum Ahmed, Krystle Nomie and Michael L. Wang

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Oncotarget. 2018; 9:25332-25341. https://doi.org/10.18632/oncotarget.25011

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Abstract

Maria I. Merolle1, Makhdum Ahmed1, Krystle Nomie1 and Michael L. Wang1

1Department of Lymphoma and Myeloma, MD Anderson Cancer Center, Houston, TX, USA

Correspondence to:

Michael L. Wang, email: miwang@mdanderson.org

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

Received: August 23, 2017     Accepted: November 05, 2017     Epub: March 27, 2018     Published: May 18, 2018

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.


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