TY - JOUR
T1 - MOLECULAR AND CLINICAL FEATURES OF CHRONIC LYMPHOCYTIC LEUKAEMIA WITH STEREOTYPED B CELL RECEPTORS: RESULTS FROM AN ITALIAN MULTICENTRIC STUDY
AU - BOMBEN, R
AU - DAL, BO M
AU - CAPELLO, Daniela
AU - FORCONI, F
AU - MAFFEI, R
AU - LAURENTI, L
AU - ROSSI, Davide
AU - MI, DEL PRINCIPE
AU - ZUCCHETTO, A
AU - BERTONI, F
AU - FM, ROSSI
AU - BULIAN, P
AU - CATTAROSSI, I
AU - ILARIUCCI, F
AU - SOZZI, E
AU - SPINA, V
AU - ZUCCA, E
AU - DEGAN, M
AU - LAURIA, F
AU - DEL, POETA G
AU - DG, EFREMOV
AU - MARASCA, R
AU - GAIDANO, Gianluca
AU - GATTEI, V.
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
UR - https://iris.uniupo.it/handle/11579/27903
U2 - 10.1111/j.1365-2141.2008.07469.x
DO - 10.1111/j.1365-2141.2008.07469.x
M3 - Article
SN - 0007-1048
VL - 144
SP - 492
EP - 506
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 4
ER -