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

Handle URI:
http://hdl.handle.net/10754/598554
Title:
Igs Expressed by Chronic Lymphocytic Leukemia B Cells Show Limited Binding-Site Structure Variability
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.
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.
Publisher:
The American Association of Immunologists
Journal:
The Journal of Immunology
KAUST Grant Number:
KUK-I1-012-43
Issue Date:
1-May-2013
DOI:
10.4049/jimmunol.1300321
PubMed ID:
23636053
Type:
Article
ISSN:
0022-1767; 1550-6606
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.
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Full metadata record

DC FieldValue Language
dc.contributor.authorMarcatili, P.en
dc.contributor.authorGhiotto, F.en
dc.contributor.authorTenca, C.en
dc.contributor.authorChailyan, A.en
dc.contributor.authorMazzarello, A. N.en
dc.contributor.authorYan, X.-J.en
dc.contributor.authorColombo, M.en
dc.contributor.authorAlbesiano, E.en
dc.contributor.authorBagnara, D.en
dc.contributor.authorCutrona, G.en
dc.contributor.authorMorabito, F.en
dc.contributor.authorBruno, S.en
dc.contributor.authorFerrarini, M.en
dc.contributor.authorChiorazzi, N.en
dc.contributor.authorTramontano, A.en
dc.contributor.authorFais, F.en
dc.date.accessioned2016-02-25T13:32:04Zen
dc.date.available2016-02-25T13:32:04Zen
dc.date.issued2013-05-01en
dc.identifier.citationMarcatili 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.en
dc.identifier.issn0022-1767en
dc.identifier.issn1550-6606en
dc.identifier.pmid23636053en
dc.identifier.doi10.4049/jimmunol.1300321en
dc.identifier.urihttp://hdl.handle.net/10754/598554en
dc.description.abstractAg 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.en
dc.description.sponsorshipThis 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.en
dc.publisherThe American Association of Immunologistsen
dc.titleIgs Expressed by Chronic Lymphocytic Leukemia B Cells Show Limited Binding-Site Structure Variabilityen
dc.typeArticleen
dc.identifier.journalThe Journal of Immunologyen
dc.contributor.institutionUniversita degli Studi di Roma La Sapienza, Rome, Italyen
dc.contributor.institutionUniversita degli Studi di Genova, Genoa, Italyen
dc.contributor.institutionFeinstein Institute for Medical Research, Manhasset, United Statesen
dc.contributor.institutionIstituto Nazionale per la Ricerca sul Cancro, Genoa, Genoa, Italyen
dc.contributor.institutionAzienda Ospedaliera di Cosenza, Cosenza, Italyen
dc.contributor.institutionNorth Shore-Long Island Jewish Health System, Great Neck, United Statesen
dc.contributor.institutionHofstra North Shore-Long Island Jewish School of Medicine, Hempstead, United Statesen
dc.contributor.institutionInstitut Pasteur - Fondazione Cenci Bolognetti, Rome, Italyen
kaust.grant.numberKUK-I1-012-43en

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