Origin of Waldenstrom's macroglobulinaemia

Waldenstrom's macroglobulinaemia (WM) is an MYD88L265P-mutated lymphoplasmacytic lymphoma that invades bone marrow and secretes monoclonal immunoglobulin M (IgM). WM cells are usually unable to undergo class switch recombination, and have mutated IGHV, with a typical immunophenotype CD19+/CD22low+/CD23-/CD25+/CD27+/CD45+/CD38low+/SmIgM+ (negative for CD5, CD10, CD11c, CD103). This immunophenotype matches memory B cells (smIgM-/+/CD10-/CD19+/CD20+/CD27+/CD38low+/CD45+), representing 30% of B cells in the blood. Fifty percent of them have not undergone class switch recombination and are IgM+. These cells have suffered somatic hypermutation as WM cells. Genetic abnormalities do not abrogate the capacity to progress to plasma cells that usually belong to the clonal WM compartment, with a normal immunophenotype and functional characteristics. However, some WM cells are CD27−, MYD88WT, without somatic hypermutation, or with class switch recombination capable of reactivation. Thus, most data support a B-memory-cell origin for WM, but a small fraction of cases may have a different origin.