Targeting Lymphomas Through MALT1 Inhibition

Lorena Fontan,Ari Melnick

doi:10.18632/oncotarget.819

Abstract

Targeting Lymphomas Through MALT1 Inhibition

Highlights

Diffuse large B-cell lymphoma (DLBCL), the most common form of non-Hodgkin Lymphoma, comprises a heterogeneous group of diseases that can be classified into at least three different entities with distinct gene expression signatures
Most notably frequent activating somatic mutation in B-cell receptor (BCR) and Toll like receptor (TLR) signaling pathways, leading to constitutive NF-κB activity [2]. Along these lines the MALT1 paracaspase has emerged as a key signaling mediator and therapeutic target in ABCDLBCLs due to its role in transducing signals from several receptors implicated in lymphomagenesis [3]
A peptide that can bind and inhibit the MALT1 catalytic pocket (Z-VRPR-FMK) was shown to downregulate NF-κB activity, suppress proliferation and induce apoptosis in activated B cell-like (ABC)-DLBCL cell lines known to contain mutations in TLR and BCR signaling components [4, 5]. These data revealed that MALT1 is a bona fide therapeutic target, inhibition of which may disrupt oncogenic signaling induced by somatic mutations in ABC-DLBCLs

Summary

Introduction

Diffuse large B-cell lymphoma (DLBCL), the most common form of non-Hodgkin Lymphoma, comprises a heterogeneous group of diseases that can be classified into at least three different entities with distinct gene expression signatures. Most notably frequent activating somatic mutation in B-cell receptor (BCR) and Toll like receptor (TLR) signaling pathways, leading to constitutive NF-κB activity [2].

Results

Conclusion