Such activation is driven by the presence of selected mutations inactivating the genes encoding negative regulators of the pathway (TRAF2, TRAF3, TNFAIP3, BIRC3, MAP3K14, CYLD, cIAP1/cIAP2) and activating the regulator molecules (NF-κB1, NF-κB2, CD40, LTβR, TACI, and NIK) in various cancer types like multiple myeloma (MM), splenic marginal zone lymphoma (SMZL), MALT lymphoma and B-cell lymphoma [15,93,145,146,147,148,149] (Table 2). This evidence concerns the gene CYLD and splenic marginal zone lymphoma.