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

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

Research output: Contribution to journalArticle

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 (≥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.

Original languageEnglish
Pages (from-to)492-506
Number of pages15
JournalBritish Journal of Haematology
Volume144
Issue number4
DOIs
Publication statusPublished - Feb 2009

Keywords

  • B cell receptor
  • Chronic lymphocytic leukaemia
  • Immunoglobulin genes
  • Prognosis

ASJC Scopus subject areas

  • Hematology

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    Bomben, R., Dal Bo, M., Capello, D., Forconi, F., Maffei, R., Laurenti, L., Rossi, D., Del Principe, M. I., Zucchetto, A., Bertoni, F., Rossi, F. M., Bulian, P., Cattarossi, I., Ilariucci, F., Sozzi, E., Spina, V., Zucca, E., Degan, M., Lauria, F., ... Gattei, V. (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. https://doi.org/10.1111/j.1365-2141.2008.07469.x