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.
Bomben
Riccardo
R
Clinical and Experimental Onco-Haematology Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano (PN), Italy.
Dal Bo
Michele
M
Capello
Daniela
D
Forconi
Francesco
F
Maffei
Rossana
R
Laurenti
Luca
L
Rossi
Davide
D
Del Principe
Maria Ilaria
MI
Zucchetto
Antonella
A
Bertoni
Francesco
F
Rossi
Francesca Maria
FM
Bulian
Pietro
P
Cattarossi
Ilaria
I
Ilariucci
Fiorella
F
Sozzi
Elisa
E
Spina
Valeria
V
Zucca
Emanuele
E
Degan
Massimo
M
Lauria
Francesco
F
Del Poeta
Giovanni
G
Efremov
Dimitar G
DG
Marasca
Roberto
R
Gaidano
Gianluca
G
Gattei
Valter
V
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D022801:Complementarity Determining Regions / Q000235:genetics; D005500:Follow-Up Studies; D015973:Gene Expression Regulation, Leukemic; D015322:Gene Rearrangement, B-Lymphocyte; D050438:Genes, Immunoglobulin Heavy Chain; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D008875:Middle Aged; D011379:Prognosis; D011947:Receptors, Antigen, B-Cell / Q000235:genetics*; D027041:Somatic Hypermutation, Immunoglobulin; D013997:Time Factors
D022801:Complementarity Determining Regions; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D011947:Receptors, Antigen, B-Cell