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    Igs Expressed by Chronic Lymphocytic Leukemia B Cells Show Limited Binding-Site Structure Variability

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    Type
    Article
    Authors
    Marcatili, P.
    Ghiotto, F.
    Tenca, C.
    Chailyan, A.
    Mazzarello, A. N.
    Yan, X.-J.
    Colombo, M.
    Albesiano, E.
    Bagnara, D.
    Cutrona, G.
    Morabito, F.
    Bruno, S.
    Ferrarini, M.
    Chiorazzi, N.
    Tramontano, A.
    Fais, F.
    KAUST Grant Number
    KUK-I1-012-43
    Date
    2013-05-01
    Online Publication Date
    2013-05-01
    Print Publication Date
    2013-06-01
    Permanent link to this record
    http://hdl.handle.net/10754/598554
    
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    Abstract
    Ag selection has been suggested to play a role in chronic lymphocytic leukemia (CLL) pathogenesis, but no large-scale analysis has been performed so far on the structure of the Ag-binding sites (ABSs) of leukemic cell Igs. We sequenced both H and L chain V(D)J rearrangements from 366 CLL patients and modeled their three-dimensional structures. The resulting ABS structures were clustered into a small number of discrete sets, each containing ABSs with similar shapes and physicochemical properties. This structural classification correlates well with other known prognostic factors such as Ig mutation status and recurrent (stereotyped) receptors, but it shows a better prognostic value, at least in the case of one structural cluster for which clinical data were available. These findings suggest, for the first time, to our knowledge, on the basis of a structural analysis of the Ab-binding sites, that selection by a finite quota of antigenic structures operates on most CLL cases, whether mutated or unmutated. Copyright © 2013 by The American Association of Immunologists, Inc.
    Citation
    Marcatili P, Ghiotto F, Tenca C, Chailyan A, Mazzarello AN, et al. (2013) Igs Expressed by Chronic Lymphocytic Leukemia B Cells Show Limited Binding-Site Structure Variability. The Journal of Immunology 190: 5771–5778. Available: http://dx.doi.org/10.4049/jimmunol.1300321.
    Sponsors
    This work was supported by Associazione Italiana Ricerca sul Cancro (IG-10698 to F.F.; IG-10492 to M.F.); Compagnia di San Paolo (4824 SD/CV, 2007.2880 to F.F.); Fondazione Maria Piaggio Casarsa, Genova, Italy (to F.G.); the National Institutes of Health (Grant RO1 CA81554 to N.C.); and King Abdullah University of Science and Technology (Grant KUK-I1-012-43 to A.T.). M.C. has a fellowship from the Associazione Italiana Ricerca sul Cancro 5 per Mille.
    Publisher
    The American Association of Immunologists
    Journal
    The Journal of Immunology
    DOI
    10.4049/jimmunol.1300321
    PubMed ID
    23636053
    ae974a485f413a2113503eed53cd6c53
    10.4049/jimmunol.1300321
    Scopus Count
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