Origin of Waldenstrom's macroglobulinaemia

Abstract

Waldenstrom's macroglobulinaemia (WM) is an MYD88^L265P-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⁺/CD22^low+/CD23^-/CD25⁺/CD27⁺/CD45⁺/CD38^low+/SmIgM⁺ (negative for CD5, CD10, CD11c, CD103). This immunophenotype matches memory B cells (smIgM^-/+/CD10^-/CD19⁺/CD20⁺/CD27⁺/CD38^low+/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^-, MYD88^WT, 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.

Keywords: B lymphocytes; Flow cytometry; Immunophenotyping; Waldenstrom's macroglobulinaemia.