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Similarities and Differences Between the Light and Heavy Chain Ig Variable Region Gene Repertoires in Chronic Lymphocytic Leukemia

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Abstract

Analyses of Ig VHDJH rearrangements expressed by B-CLL cells have provided insights into the antigen receptor repertoire of B-CLL cells and the maturation stages of B-lymphocytes that give rise to this disease. However, less information is available about the L chain V gene segments utilized by B-CLL cells and to what extent their characteristics resemble those of the H chain. We analyzed the VL and JL gene segments of 206 B-CLL patients, paying particular attention to frequency of use and association, mutation status, and LCDR3 characteristics. Approximately 40% of B-CLL cases express VL genes that differ significantly from their germline counterparts. Certain genes were virtually always mutated and others virtually never. In addition, preferential pairing of specific VL and JL segments was found. These findings are reminiscent of the expressed VH repertoire in B-CLL. However unlike the VH repertoire, VL gene use was not significantly different than that of normal B-lymphocytes. In addition, Vκ genes that lie more upstream on the germline locus were less frequently mutated than those at the 3′ end of the locus; this was not the case for Vλ genes and is not for VH genes. These similarities and differences between the IgH and IgL V gene repertoires expressed in B-CLL suggest some novel features while also reinforcing concepts derived from studies of the IgH repertoire.

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Acknowledgments

These studies were supported in part by the National Institutes of Health via RO1 grants from the National Cancer Institute (CA81554 and CA87956), a General Clinical Research Center Grant (M01 RR018535) from the National Center for Research Resources, and by Associazione Italiana per la Ricerca sul Cancro (AIRC) and FIRB (RBNE01A4Y9/004). The Karches Family Foundation, the Peter J. Sharp Foundation, the Marks Family Foundation, the Jean Walton Fund for Lymphoma & Myeloma Research, and the Joseph Eletto Leukemia Research Fund also provided support.

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Authors and Affiliations

  1. Department of Medicine, North Shore University Hospital, Manhasset, NY, USA

    Fabio Ghiotto, Franco Fais, Angelo Valetto, Jonathan E Kolitz, Steven L Allen & Nicholas Chiorazzi

  2. Department of Experimental Medicine, Human Anatomy Section, University of Genoa, Via De Toni 14, 16132, Genoa, Italy

    Fabio Ghiotto & Franco Fais

  3. North Shore - LIJ Health System, The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY, USA

    Emilia Albesiano, Cristina Sison, Janine Reinhardt, Jonathan E Kolitz, Kanti Rai, Steven L Allen & Nicholas Chiorazzi

  4. Department of Medical Sciences and IRCAD, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy

    Gianluca Gaidano

  5. Department of Medicine, NYU School of Medicine, New York, NY, USA

    Jonathan E Kolitz & Steven L Allen

  6. Department of Medicine, Long Island Jewish Medical Center, 270-05 76th Avenue, New Hyde Park, NY, USA

    Kanti Rai

  7. Department of Medicine, Albert Einstein School of Medicine, Bronx, NY, USA

    Kanti Rai & Nicholas Chiorazzi

  8. Division of Medical Oncology C, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy

    Manlio Ferrarini

  9. Dipartimento di Oncologia Clinica e Sperimentale, Universitá di Genova, Genova, Italy

    Manlio Ferrarini

  10. Department of Cell Biology, Albert Einstein School of Medicine, Bronx, NY, USA

    Nicholas Chiorazzi

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  1. Fabio Ghiotto
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  2. Franco Fais
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  3. Emilia Albesiano
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  8. Jonathan E Kolitz
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  9. Kanti Rai
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Correspondence to Fabio Ghiotto.

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Ghiotto, F., Fais, F., Albesiano, E. et al. Similarities and Differences Between the Light and Heavy Chain Ig Variable Region Gene Repertoires in Chronic Lymphocytic Leukemia. Mol Med 12, 300–308 (2006). https://doi.org/10.2119/2006-00080.Ghiotto

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