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

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Molecular and clinical features of chronic lymphocytic leukaemia with

stereotyped B cell receptors: results from an Italian multicentre study.

Riccardo Bomben, Michele Dal Bo, a Capello, Francesco Forconi, Rossana

Maffei, Luca ti, e Rossi, Ilaria Del Principe, Antonella

Zucchetto, Francesco Bertoni, Francesca Rossi, Pietro Bulian, Ilaria

Cattarossi, Fiorella Ilariucci, Sozzi, Valeria Spina, Emanuele Zucca,

Massimo Degan, Francesco Lauria, Giovanni Del Poeta, Dimitar G Efremov, o

Marasca, Gianluca Gaidano, and Valter Gattei

Br J Haematol, November 19, 2008; .

Clinical and Experimental Onco-Haematology Unit, Centro di Riferimento

Oncologico, I.R.C.C.S., Aviano (PN), Italy.

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.

PMID: 19036101