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Blood, 1 October 2004, Vol. 104, No. 7, pp. 2134-2142. Prepublished online as a Blood First Edition Paper on February 5, 2004; DOI 10.1182/blood-2003-11-4024. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-11-4024v1 104/7/2134    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kriangkum, J. Articles by Pilarski, L. M. Search for Related Content PubMed PubMed Citation Articles by Kriangkum, J. Articles by Pilarski, L. M. Related Collections Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Clonotypic IgM V/D/J sequence analysis in Waldenstrom macroglobulinemia suggests an unusual B-cell origin and an expansion of polyclonal B cells in peripheral blood Jitra Kriangkum, Brian J. Taylor, Steven P. Treon, Michael J. Mant, Andrew R. Belch, and Linda M. Pilarski From the Departments of Medicine, Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada; and the Department of Hematologic Oncology, Dana-Farber Cancer Institute, Boston, MA. Analysis of clonotypic immunoglobulin M (IgM) from 15 patients with Waldenstrom macroglobulinemia (WM) showed a strong preferential use of the VH3/JH4 gene families. Identification of the WM IgM V/D/J was validated using single-cell analysis, confirming its presence in most B cells. Despite the extensive hypermutated VH genes in 13 of 15 patients, statistical analysis of framework/complementary-determining region (FR/CDR) mutation patterns suggests that they might have escaped antigenic selection. Neither intraclonal diversity nor isotype switching was detectable. Membranous and secreted forms of clonotypic IgM transcripts were present in bone marrow and blood. Single-cell analysis showed that clonotypic B cells coexpress CD20, surface IgM (sIgM), and sIgD but that they lack CD138. Most B cells lacked memory marker CD27 despite their hypermutated variable regions otherwise suggestive of memory status. At diagnosis, circulating B cells in WM are largely clonotypic. However, when monoclonal IgM levels are decreased, clonotypic frequencies are substantially reduced despite elevated CD20+ cells, shown to be polyclonal by DNA sequencing and CDR3 fragment analysis. Thus, WM includes the expansion of circulating, polyclonal B cells. Overall, this work suggests that WM may originate from a largely VH3-restricted, somatically mutated, predominantly CD27-IgM+IgD+ population that cannot undergo class switching, suggestive of B cells that might have bypassed the germinal center. (Blood. 2004;104:2134-2142) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Berentsen Rituximab for the treatment of autoimmune cytopenias Haematologica, December 1, 2007; 92(12): 1589 - 1596. [Full Text] [PDF] A. Vijay and M. A. Gertz Waldenstrom macroglobulinemia Blood, June 15, 2007; 109(12): 5096 - 5103. [Abstract] [Full Text] [PDF] C. Wei, J. Anolik, A. Cappione, B. Zheng, A. Pugh-Bernard, J. Brooks, E.-H. Lee, E. C. B. Milner, and I. Sanz A New Population of Cells Lacking Expression of CD27 Represents a Notable Component of the B Cell Memory Compartment in Systemic Lupus Erythematosus J. Immunol., May 15, 2007; 178(10): 6624 - 6633. [Abstract] [Full Text] [PDF] P. Martin-Jimenez, R. Garcia-Sanz, A. Balanzategui, M. Alcoceba, E. Ocio, M{a} L. Sanchez, M. Gonzalez, and J. San Miguel Molecular characterization of heavy chain immunoglobulin gene rearrangements in Waldenstrom's macroglobulinemia and IgM monoclonal gammopathy of undetermined significance Haematologica, May 1, 2007; 92(5): 635 - 642. [Abstract] [Full Text] [PDF] J. Kriangkum, B. J. Taylor, S. P. Treon, M. J. Mant, T. Reiman, A. R. Belch, and L. M. Pilarski Molecular Characterization of Waldenstrom's Macroglobulinemia Reveals Frequent Occurrence of Two B-Cell Clones Having Distinct IgH VDJ Sequences Clin. Cancer Res., April 1, 2007; 13(7): 2005 - 2013. [Abstract] [Full Text] [PDF] W. J. Chng, R. F. Schop, T. Price-Troska, I. Ghobrial, N. Kay, D. F. Jelinek, M. A. Gertz, A. Dispenzieri, M. Lacy, R. A. Kyle, et al. Gene-expression profiling of Waldenstrom macroglobulinemia reveals a phenotype more similar to chronic lymphocytic leukemia than multiple myeloma Blood, October 15, 2006; 108(8): 2755 - 2763. [Abstract] [Full Text] [PDF] J. Kriangkum, B. J. Taylor, E. Strachan, M. J. Mant, T. Reiman, A. R. Belch, and L. M. Pilarski Impaired class switch recombination (CSR) in Waldenstrom macroglobulinemia (WM) despite apparently normal CSR machinery Blood, April 1, 2006; 107(7): 2920 - 2927. [Abstract] [Full Text] [PDF]

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