The malignant clone in Waldenstrom's macroglobulinemia☆☆☆★

Abstract 

The unique IgM VDJ sequence that characterizes the malignant clone in Waldenstrom's macroglobulinemia (WM), termed clonotypic, was identified for 12 WM patients. The majority of WM patients (92%) had a clonotypic IgM from the VH3 family, with predominantly long CDR3 regions, characteristic of those found in antigen-stimulated populations. Clonotypic IgM transcripts were detected in both blood and bone marrow (BM), clearly identifying a blood-borne compartment of WM. Abnormal numbers of CD20⁺ B cells were usually detectable and expressed surface IgM. In most cases these cells also expressed surface IgD. Most WM patients lacked detectable CD138⁺ plasma cells in either blood or BM. Longitudinal analysis suggests that phenotypic identification of B cells in blood of WM patients is insufficient for monitoring disease. Although serum IgM had decreased and clonotypic transcripts were very weak for one patient, the number of CD20⁺ B cells increased dramatically. The lack of clonotypic transcripts suggests that the majority of these circulating B cells were polyclonal and were not part of the WM clone, indicating that monitoring of clonotypic IgM provides the most accurate identifier of WM cells. Semin Oncol 30:132-135. © 2003 Elsevier Inc. All rights reserved.