Acquired CARD11 mutation promotes BCR independence in Diffuse Large B Cell Lymphoma.
Diffuse large B cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma that is molecularly and clinically heterogeneous. Gene expression studies have revealed how DLBCL can be divided into germinal center (GC) and activated B cell (ABC) subtypes. The ABC subtype is associated with constitutive activation of the NF-κB pathway, commonly as a consequence of genetic activation of the B cell receptor (BCR) pathway1. Components of the BCR pathway that are activated by mutation include CD79B, MYD88 and CARD11. Chronic stimulation of the BCR in ABC DLBCL may also result from engagement of the BCR by self antigens in the tumor microenvironment. These preclinical observations suggest a role for the targeted inhibitors of the BCR pathway in the treatment of DLBCL1.
Wellcome Trust (203151/Z/16/Z)
Medical Research Council (MC_PC_17230)