MYD88 L265P mutation
MYD88 L265P mutation appears to be the most frequent mutation described to date in WM (91% of cases). MYD88 L265P mutation may be considered as the first genetic hit in Waldeström Macroglobulinemia that promotes NF-κB and JAK-STAT3 signaling and subsequently initiates alteration of major pathways, such as apoptotic pathways.
The diagnostic discrimination of WM/lymphoplasmacytic lymphoma (LPL) versus marginal zone lymphomas (MZLs), IgM secreting myeloma (MM), and chronic lymphocytic leukemia (CLL) with plasmacytic differentiation can sometimes be difficult due to overlapping clinicopathological characteristics. MYD88 L265P can help distinguish WM/LPL from MZL, MM, and CLL, which show no or infrequent expression (3% to 9%) of this somatic mutation, with the possibility that many of these cases are WM/LPL
