Alternative hypotheses proposed for the MYD88 L265P mutation in IgM-MGUS and WM pathogenesis. (A) MYD88 L265P mutation is a critical and universal progression event from IgM-MGUS to WM. (B) There are various biologic subtypes of IgM MGUS, and the MYD88 L265P mutation is found in the subtype that originates WM.