Targeting the B-cell receptor pathway in diffuse large B-cell lymphoma

Abstract

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous diagnostic category with different molecular subtypes defined by distinct gene expression patterns and divergent mechanisms of oncogenic activation. Several studies have suggested an inferior survival for patients of the activated B-cell-like (ABC) versus the germinal center B-cell-like (GCB) DLBCL subtype which has led to increasing interest in investigating pharmacological inhibition of signaling pathways which contribute to lymphomagenesis and that are specifically utilized by ABC DLBCL cells. One of these signaling cascades is the B-cell receptor (BCR) pathway and several approaches in clinical trials to target this cascade have demonstrated promising therapeutic activity. This review discusses our current understanding of the role of BCR signaling in different DLBCL subtypes, including primary central nervous system lymphoma (PCNSL), a subgroup of DLBCL that is particularly dependent on BCR signaling. One specific aim of this review is to highlight novel approaches to therapeutically target BCR signaling in DLBCL.

Keywords: B-cell receptor signaling; BTK; DLBCL; PCNSL; PI3K.