Distribution of t(14;18)-positive, putative lymphoma precursor cells among B-cell subsets in healthy individuals

Authors

  • Carsten Hirt,

    1. Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA
    2. Department of Hematology and Oncology, Greifswald University Medical Center, Greifswald, Germany
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  • Gottfried Dölken,

    1. Department of Hematology and Oncology, Greifswald University Medical Center, Greifswald, Germany
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  • Siegfried Janz,

    1. Laboratory of Genetics, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA
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  • Charles S. Rabkin

    1. Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA
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  • Presented in abstract form at the 97th Annual Meeting of the American Association for Cancer Research, Washington, DC, April 4, 2006.

Carsten Hirt, Klinik und Poliklinik für Innere Medizin C, Hämatologie und Onkologie, Transplantationszentrum, Universitätsklinikum Greifswald, Sauerbruchstrasse, D-17487 Greifswald, Germany.
E-mail: hirtonko@uni-greifswald.de

Summary

The t(14;18)(q32;q21) is the characteristic chromosomal translocation of follicular lymphoma (FL). Highly sensitive polymerase chain reaction (PCR) techniques can also detect t(14;18)-sequences in the blood and lymphoid tissues of healthy individuals (HI). The aim of this study was to determine the immunophenotypic markers of t(14;18)-positive cells in HI and to relate these features to lymphocyte maturation. B cells from 10 subjects with t(14;18)-positive and three subjects with t(14;18)-negative peripheral blood mononuclear cells (PBMC) were fluorescence-activated cell sorted for antigen-naïve (CD27), immunoglobulin M (IgM) memory (IgM+CD27+) and switched memory (IgM CD27+) cells. t(14;18)-recombinations were detected by quantitative PCR. Among PBMC-positive subjects, t(14;18)-frequency was significantly higher in IgM memory (median: 380/106) than in antigen-naïve (median: 16/106) or switched memory (median: 5/106) B cells. All PBMC-negative subjects nevertheless had detectable t(14;18) in sorted B cells; levels were lower than in PBMC-positive subjects, but had the same relative predominance. These results suggest that t(14;18) is generated during early B-cell development in the bone marrow and that affected cells may mature and expand in germinal centres. t(14;18)-frequency was highest in IgM memory cells, a B-cell subset that shares immunophenotypic similarities with FL. The significance of these cells as lymphoma precursors or indicators of lymphoma risk remains to be established.

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