Previously published work provides a rationale for the design of therapies targeting the alternative NF-kB pathway in a fraction of DLBCL patients and suggests that for those human DLBCLs that display both canonical and alternative NF-kB mutations [88, 90], both alternative or canonical of NF-kB signaling may be required for therapeutic intervention, as recently demonstrated for multiple myeloma [219]. This evidence concerns the gene NFKB1 and diffuse large B-cell lymphoma.