In this study, we used IGH sequence analysis to assess the maturational status of Waldenstrom's (WM) macroglobulinemia and its putative precursor immunoglobulin (Ig)-M monoclonal gammopathy of undetermined significance (MGUS). IGH sequence analysis was performed using standard methods in 23 cases (20 WM and 3 IgM MGUS as defined by consensus panel criteria). Waldenstrom's macroglobulinemia cases were characterized by heavily mutated IGH genes (median, 6.3%; range, 3.8%-13.9%) but without intraclonal variation (ICV). IgM MGUS was similarly characterized by somatic hypermutation (median, 7.5%; range, 7%-7.7%), but ICV was evident in 1 of the 3 cases. We would therefore conclude that WM is characterized by somatic hypermutation without ICV, which supports a derivation from postgerminal center/memory B cells. IgM MGUS is also characterized by somatic hypermutation but, in a manner similar to IgA/IgG MGUS, can be associated with ICV, although the significance of this remains unclear.
- Gene Rearrangement
- Immunoglobulin Heavy Chains
- Immunoglobulin M
- Middle Aged
- Sequence Analysis, DNA
- Waldenstrom Macroglobulinemia
Rollett, R. A., Wilkinson, E. J., Gonzalez, D., Fenton, J. A., Short, M. A., Evans, P. A., Rawstron, A. C., & Owen, R. G. (2006). Immunoglobulin heavy chain sequence analysis in Waldenstrom's macroglobulinemia and immunoglobulin M monoclonal gammopathy of undetermined significance. CLINICAL LYMPHOMA & MYELOMA, 7(1), 70-72. https://doi.org/10.3816/CLM.2006.n.042