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Molecular and clinical features of chronic lymphocytic leukaemia with stereotyped B cell receptors: results from an Italian multicentre study

Molecular and clinical features of chronic lymphocytic leukaemia with stereotyped B cell receptors: results from an Italian multicentre study
Molecular and clinical features of chronic lymphocytic leukaemia with stereotyped B cell receptors: results from an Italian multicentre study
A fraction of chronic lymphocytic leukaemia (CLL) cases carry highly homologous B-cell receptors (BCR), i.e. characterized by non-random combinations of immunoglobulin heavy-chain variable (IGHV) genes and heavy-chain complementarity determining region-3 (HCDR3), often associated with a restricted selection of IGVK/L light chains. Such 'stereotyped' BCR occur more frequently in CLL with unmutated (UM) than mutated (M) IGHV genes. We analysed 1426 IG rearrangements (from 1398 CLL cases) by a clustering driven by HCDR3 similarities. Molecular findings were correlated to time-to-treatment (TTT) and presence of known prognosticators. Sixty-nine clusters (319 IG-rearrangements, 22.4%) with stereotyped BCR were identified. Among 30 confirmed clusters (>or=3 IG-rearrangements/cluster), we found 14 novel clusters, of which 11 had M IG rearrangements (M clusters) and predominantly (8/11) used IGHV3 subgroup genes. Recurrent cluster-biased amino acid changes were found throughout IGHV sequences of these 'M clusters'. Regarding clinical outcome: (i) UM CLL from the IGHV1-2/1-3/1-18/1-46/7-4-1/IGKV1-39 cluster had poorer prognosis than UM/M cases, or UM cases using the same IGHV genes but not in clusters; (ii) M CLL from the IGHV3-21/IGLV3-21 cluster had TTT similar to UM CLL, and shorter than M CLL expressing IGHV3-21 but not in cluster. Altogether, our analysis identified additional molecular and clinical features for CLL expressing stereotyped BCR.
chronic lymphocytic leukaemia, B cell receptor, immunoglobulin genes, prognosis
0007-1048
492-506
Bomben, Riccardo
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Dal Bo, Michele
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Capello, Daniela
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Forconi, Francesco
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Maffei, Rossana
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Laurenti, Luca
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Rossi, Davide
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Del Principe, Maria Ilaria
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Zucchetto, Antonella
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Bertoni, Francesco
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Rossi, Francesca Maria
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Bulian, Pietro
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Cattarossi, Ilaria
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Ilariucci, Fiorella
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Sozzi, Elisa
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Spina, Valeria
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Zucca, Emanuele
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Degan, Massimo
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Lauria, Francesco
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Del Poeta, Giovanni
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Efremov, Dimitar G.
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Marasca, Roberto
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Gaidano, Gianluca
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Gattei, Valter
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Bomben, Riccardo
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Dal Bo, Michele
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Capello, Daniela
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Forconi, Francesco
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Maffei, Rossana
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Laurenti, Luca
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Rossi, Davide
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Del Principe, Maria Ilaria
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Zucchetto, Antonella
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Bertoni, Francesco
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Rossi, Francesca Maria
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Bulian, Pietro
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Cattarossi, Ilaria
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Ilariucci, Fiorella
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Sozzi, Elisa
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Spina, Valeria
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Zucca, Emanuele
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Degan, Massimo
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Lauria, Francesco
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Del Poeta, Giovanni
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Efremov, Dimitar G.
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Marasca, Roberto
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Gaidano, Gianluca
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Gattei, Valter
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Bomben, Riccardo, Dal Bo, Michele, Capello, Daniela, Forconi, Francesco, Maffei, Rossana, Laurenti, Luca, Rossi, Davide, Del Principe, Maria Ilaria, Zucchetto, Antonella, Bertoni, Francesco, Rossi, Francesca Maria, Bulian, Pietro, Cattarossi, Ilaria, Ilariucci, Fiorella, Sozzi, Elisa, Spina, Valeria, Zucca, Emanuele, Degan, Massimo, Lauria, Francesco, Del Poeta, Giovanni, Efremov, Dimitar G., Marasca, Roberto, Gaidano, Gianluca and Gattei, Valter (2009) Molecular and clinical features of chronic lymphocytic leukaemia with stereotyped B cell receptors: results from an Italian multicentre study. British Journal of Haematology, 144 (4), 492-506. (doi:10.1111/j.1365-2141.2008.07469.x). (PMID:19036101)

Record type: Article

Abstract

A fraction of chronic lymphocytic leukaemia (CLL) cases carry highly homologous B-cell receptors (BCR), i.e. characterized by non-random combinations of immunoglobulin heavy-chain variable (IGHV) genes and heavy-chain complementarity determining region-3 (HCDR3), often associated with a restricted selection of IGVK/L light chains. Such 'stereotyped' BCR occur more frequently in CLL with unmutated (UM) than mutated (M) IGHV genes. We analysed 1426 IG rearrangements (from 1398 CLL cases) by a clustering driven by HCDR3 similarities. Molecular findings were correlated to time-to-treatment (TTT) and presence of known prognosticators. Sixty-nine clusters (319 IG-rearrangements, 22.4%) with stereotyped BCR were identified. Among 30 confirmed clusters (>or=3 IG-rearrangements/cluster), we found 14 novel clusters, of which 11 had M IG rearrangements (M clusters) and predominantly (8/11) used IGHV3 subgroup genes. Recurrent cluster-biased amino acid changes were found throughout IGHV sequences of these 'M clusters'. Regarding clinical outcome: (i) UM CLL from the IGHV1-2/1-3/1-18/1-46/7-4-1/IGKV1-39 cluster had poorer prognosis than UM/M cases, or UM cases using the same IGHV genes but not in clusters; (ii) M CLL from the IGHV3-21/IGLV3-21 cluster had TTT similar to UM CLL, and shorter than M CLL expressing IGHV3-21 but not in cluster. Altogether, our analysis identified additional molecular and clinical features for CLL expressing stereotyped BCR.

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e-pub ahead of print date: 19 November 2008
Published date: February 2009
Keywords: chronic lymphocytic leukaemia, B cell receptor, immunoglobulin genes, prognosis
Organisations: Cancer Sciences

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Local EPrints ID: 358155
URI: https://eprints.soton.ac.uk/id/eprint/358155
ISSN: 0007-1048
PURE UUID: 9fe7ebc0-daba-45be-97c2-10042e4d7a7f

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Date deposited: 08 Oct 2013 13:26
Last modified: 16 Jul 2019 21:21

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Contributors

Author: Riccardo Bomben
Author: Michele Dal Bo
Author: Daniela Capello
Author: Rossana Maffei
Author: Luca Laurenti
Author: Davide Rossi
Author: Maria Ilaria Del Principe
Author: Antonella Zucchetto
Author: Francesco Bertoni
Author: Francesca Maria Rossi
Author: Pietro Bulian
Author: Ilaria Cattarossi
Author: Fiorella Ilariucci
Author: Elisa Sozzi
Author: Valeria Spina
Author: Emanuele Zucca
Author: Massimo Degan
Author: Francesco Lauria
Author: Giovanni Del Poeta
Author: Dimitar G. Efremov
Author: Roberto Marasca
Author: Gianluca Gaidano
Author: Valter Gattei

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