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

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.

DOI: 10.1111/j.1365-2141.2008.07469.x

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@article{Bomben2009MolecularAC, title={Molecular and clinical features of chronic lymphocytic leukaemia with stereotyped B cell receptors: results from an Italian multicentre study.}, author={Riccardo Bomben and Michele Dal Bo and D. Capello and Francesco Forconi and Rossana Maffei and Luca Laurenti and Davide Rossi and Maria Ilaria del Principe and Antonella Zucchetto and Francesco Bertoni and Francesca Rossi and Pietro Bulian and Ilaria Cattarossi and Fiorella Ilariucci and Elisa Sozzi and Valeria Spina and Emanuele Zucca and Massimo Degan and Francesco Nicola Lauria and Giovanni del Poeta and Dimitar G Efremov and Roberto Marasca and Gianluca Gaidano and Valter Gattei}, journal={British journal of haematology}, year={2009}, volume={144 4}, pages={492-506} }