Oncogenic MYD88 mutation drives Toll pathway to lymphoma

Abstract

MYD88 is an adaptor protein through which most of the Toll-like receptors (TLRs) and receptors for interleukin (IL)-1 and IL-18 cytokines signal.1 MYD88 transduces signals to the nuclear factor κB (NFκB) transcription factors that, in turn, regulate the production of cytokines and anti-apoptotic molecules. In mice, MYD88 deficiency impairs immunity to a range of microorganisms, and in humans absence of MYD88 results in life-threatening recurrent pyogenic bacterial infections.2, 3 Given the central role of MYD88 and TLRs in immunity, overactivity of this pathway has been associated with autoimmune diseases and now, for the first time, TLR signalling is implicated in lymphomagenesis. In a recent Nature letter, Ngo et al.4 report that gain-of-function mutations in MYD88 drive a substantial percentage of B-cell lymphomas. This study demonstrates the need for developing pharmacological inhibitors targeting MYD88 and other components of the Toll pathway in lymphomas.