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.

Bomben, R., Dal Bo, M., Capello, D., Forconi, F., Maffei, R., Laurenti, L., et al. (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 [10.1111/j.1365-2141.2008.07469.x].

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

DEL PRINCIPE, MARIA ILARIA;DEL POETA, GIOVANNI;
2009-02-01

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.
feb-2009
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/15 - MALATTIE DEL SANGUE
English
Con Impact Factor ISI
Humans; Prognosis; Aged; Receptors, Antigen, B-Cell; Complementarity Determining Regions; Gene Expression Regulation, Leukemic; Somatic Hypermutation, Immunoglobulin; Leukemia, Lymphocytic, Chronic, B-Cell; Aged, 80 and over; Adult; Chromosome Aberrations; Immunoglobulin Variable Region; Middle Aged; Follow-Up Studies; Genes, Immunoglobulin Heavy Chain; Immunoglobulin Heavy Chains; Time Factors; Immunophenotyping; Gene Rearrangement, B-Lymphocyte
Bomben, R., Dal Bo, M., Capello, D., Forconi, F., Maffei, R., Laurenti, L., et al. (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 [10.1111/j.1365-2141.2008.07469.x].
Bomben, R; Dal Bo, M; Capello, D; Forconi, F; Maffei, R; Laurenti, L; Rossi, D; DEL PRINCIPE, Mi; Zucchetto, A; Bertoni, F; Rossi, F; Bulian, P; Cattarossi, I; Ilariucci, F; Sozzi, E; Spina, V; Zucca, E; Degan, M; Lauria, F; DEL POETA, G; Efremov, D; Marasca, R; Gaidano, G; Gattei, V
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/40758
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