Except for TLR3, NF-κB activation by TLRs depends on the adaptor protein, MYD88, which is frequently targeted by gain-of-function mutations in hematological malignancies, such as DLBCL of the activated B-cell (ABC) subtype (ABC-DLBCL) and Waldenström’s macroglobulinemia (WM), where the oncogenic MYD88L265P mutation was shown to occur in over 30% and 90% of case, respectively [57]. The gene discussed is NFKB1; the disease is diffuse large B-cell lymphoma.