Genetic Mutation May Be Exclusive to Waldenström's Macroglobulinemia

Researchers have identified a genetic mutation that appears to be almost exclusive to patients diagnosed with the lymphoplasmacytic lymphoma Waldenström's macroglobulinemia, one not typically found in patients with other lymphoid cancers of B-cell origin.

Waldenström's macroglobulinemia is an indolent non-Hodgkin's lymphoma where IgM—Immunoglobin M, an antibody produced by B-cells is secreted, allowing for lymphoplasmacytic cells to enter the bone marrow and cause the blood to become too viscous, or thick.

Dana-Farber Cancer Institute researchers carried out whole genome sequencing of 30 patients with Waldenström's macroglobulinemia and found a a single nucleotide variant mutation in MYD88 L265P in 26 of them, according to findings published in the New England Journal of Medicine.

More accurate diagnoses

Identification of this mutation means that it may become useful in making more accurate diagnoses between lymphoplasmacytic lymphomas like Waldenström's macroglobulinemia and cancers which seem to share morphologic, immunophenotypic, cytogenetic and clinical features with them, such as marginal-zone lymphoma and multiple myeloma.

In a disorder known as IgM-associated gammopathy of unknown significance (MGUS), the IgM is secreted but does not affect the bone marrow. In some cases this progresses into Waldenström's macroglobulinemia. What causes this progression is not known, but further sequencing demonstrated that the mutation is not presentin MGUS patients, leading researchers to note that "It is tempting to speculate that acquisition of MYD88 L265P represents a transforming event that facilitates the progression of IgM MGUS to Waldenström's macroglobulinemia."

Sources: NEJM, MedPage Today