Lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia derives from an extensively hypermutated B cell that lacks ongoing somatic hypermutation

Walsh, Sarah H.; Laurell, Anna; Sundström, Gunnel; Roos, Göran; Sundström, Christer; Rosenquist, Richard

doi:10.1016/j.leukres.2004.12.008

« Previous Next »Leukemia Research
Volume 29, Issue 7 , Pages 729-734, July 2005

Lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia derives from an extensively hypermutated B cell that lacks ongoing somatic hypermutation

Sarah H. Walsh
- Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, SE-75185 Uppsala, Sweden
Anna Laurell
- Department of Oncology, Radiology, and Clinical Immunology, Uppsala University, Uppsala, Sweden
Gunnel Sundström
- Department of Internal Medicine, Section of Haematology, Norrlands University Hospital, Umeå, Sweden
Göran Roos
- Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden
Christer Sundström
- Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, SE-75185 Uppsala, Sweden
Richard Rosenquist
- Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, SE-75185 Uppsala, Sweden
- Corresponding author. Tel.: +46 18 6115947; fax: +46 18 554025.

Received 6 September 2004; accepted 17 December 2004. published online 07 March 2011.

Abstract

Lymphoplasmacytic lymphoma (LPL) is a rare lymphoma thought to originate from a B cell stimulated to differentiate to a plasma cell, and which is usually accompanied by clonal IgM secretion, defining the diagnosis of Waldenström's macroglobulinemia (WM). However, the immunoglobulin variable heavy chain (V_H) gene usage and the somatic hypermutation status have not been widely investigated in LPL. LPL biopsies (CD19⁺/CD20⁺/CD22⁺/CD5⁻/CD10⁻/CD23⁻/κ⁺) from 14 patients were included most of whom had a serum IgM component of variable magnitude (two cases with IgG). Highly mutated V_H genes (mean mutation rate 8%) were revealed in 13 of 14 LPLs, whereas one case displayed a germline V_H gene configuration. Cloning of the V_H gene rearrangements in nine cases showed homogeneous sequences without intraclonal heterogeneity. Furthermore, no bias in the V_H gene usage was shown, with V_H3, V_H4, and V_H1 gene family members represented. These data confirm that the LPL precursor cell has been exposed to the germinal centre environment, as indicated by extensive hypermutation, but also that the transformation event occurred after affinity maturation, since there was a lack of intraclonal variation. Additionally, the V_H gene repertoire was not skewed in LPL/WM as has been demonstrated in other B cell malignancies.