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Genetic Profile of Waldenström Macroglobulinemia

WM is related more closely to chronic lymphocytic leukemia than to multiple myeloma.

Waldenström macroglobulinemia (WM) is a unique B-cell neoplasm typified by lymphoplasmatic proliferation involving the marrow and the production of IgM paraprotein, often leading to symptomatic blood hyperviscosity. No standard therapy is curative; typical treatment regimens are similar to those for indolent lymphoma and chronic lymphocytic leukemia (CLL). No recurring cytogenetic abnormalities have been found, and the specific relation of WM to plasma-cell dyscrasias and CLL is uncertain. Researchers performed gene-expression profiling analyses of neoplastic cells from 23 patients with WM, 8 with CLL, 22 with monoclonal gammopathy of undetermined significance (MGUS), 24 with smoldering myeloma, and 101 with multiple myeloma (MM). Normal B-cells and plasma cells were assayed as controls. Cells were purified from peripheral blood and marrow samples by selection with immunomagnetic beads.

The WM expression profiles were largely homogeneous, consistent with common pathogenetic mechanisms among WM cases. Comparative analysis across the analyzed disease types demonstrated that the composite WM profile was most similar to that of CLL (rather than to those of the plasma-cell disorders). In addition, most WM cells expressed a group of genes that included the gene for interleukin-6 (IL-6), which suggests a role for cytokine-associated pathogenesis.

Comment: These findings provide strong evidence that WM falls within the spectrum of indolent B-cell neoplasms and that mechanisms similar to CLL underlie its biology. Current management approaches range from watchful waiting for asymptomatic patients to prescribing rituximab-, alkylator-, or nucleoside analogue–based therapies, with plasmapheresis for symptomatic patients with elevated IgM levels and associated hyperviscosity. These new insights provide leads for investigations of pathogenesis and suggest logical therapeutic targets, including IL-6.

— Michael E. Williams, MD

Published in Journal Watch Oncology and Hematology November 27, 2006

Citation(s):

Chng WJ et al. Gene-expression profiling of Waldenström macroglobulinemia reveals a phenotype more similar to chronic lymphocytic leukemia than multiple myeloma. Blood 2006 Oct 15; 108:2755-63.

• Original article (Subscription may be required)
• Medline abstract (Free)

Wiestner A. Gene expression relates WM to CLL. Blood 2006 Oct 15; 108:2499-500.

• Original article (Subscription may be required)