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

被引：97

作者：

Bomben, Riccardo ^{[1
]}

Dal Bo, Michele ^{[1
]}

Capello, Daniela ^{[2
,3
]}

Forconi, Francesco ^{[4
]}

Maffei, Rossana ^{[5
]}

Laurenti, Luca ^{[6
]}

Rossi, Davide ^{[2
,3
]}

Del Principe, Maria Ilaria ^{[7
]}

Zucchetto, Antonella ^{[1
]}

Bertoni, Francesco ^{[8
,9
]}

Rossi, Francesca Maria ^{[1
]}

Bulian, Pietro ^{[1
]}

Cattarossi, Ilaria ^{[1
]}

Ilariucci, Fiorella ^{[10
]}

Sozzi, Elisa ^{[4
]}

Spina, Valeria ^{[2
,3
]}

Zucca, Emanuele ^{[8
,9
]}

Degan, Massimo ^{[1
]}

Lauria, Francesco ^{[4
]}

Del Poeta, Giovanni ^{[7
]}

Efremov, Dimitar G. ^{[11
]}

Marasca, Roberto ^{[5
]}

Gaidano, Gianluca ^{[2
,3
]}

Gattei, Valter ^{[1
]}

机构：

[1] IRCCS, Ctr Riferimento Oncol, Clin & Expt Oncohaematol Unit, I-33081 Aviano, PN, Italy

[2] Amedeo Avogadro Univ Eastern Piedmont, Div Haematol, Dept Clin & Expt Med, Novara, Italy

[3] Amedeo Avogadro Univ Eastern Piedmont, BRMA, Novara, Italy

[4] Univ Siena, Dept Clin Med & Immunol Sci, Div Haematol & Transplant, I-53100 Siena, Italy

[5] Univ Modena & Reggio Emilia, Div Haematol, Dept Haematol & Oncol, Modena, Italy

[6] Univ Cattolica Sacro Cuore, Haematol Inst, Rome, Italy

[7] Univ Tor Vergata, S Eugenio Hosp, Div Haematol, Rome, Italy

[8] Oncol Inst So Switzerland, Expt Oncol Lab, Bellinzona, Switzerland

[9] Oncol Inst So Switzerland, Lymphoma Unit, Bellinzona, Switzerland

[10] Reggio Emilia Hosp, Haematol Unit, Modena, Italy

[11] ICGEB Outstn Monterotondo, Rome, Italy

来源：

BRITISH JOURNAL OF HAEMATOLOGY | 2009年 / 144卷 / 04期

关键词：

chronic lymphocytic leukaemia; B cell receptor; immunoglobulin genes; prognosis; VARIABLE-REGION MUTATIONS; ANTIGEN-DRIVEN SELECTION; V-H; CD38; EXPRESSION; SOMATIC HYPERMUTATION; ZAP-70; GENE-MUTATIONS; PATHOGENETIC IMPLICATIONS; NATURAL AUTOANTIBODIES; IMMUNOGLOBULIN HEAVY;

D O I：

10.1111/j.1365-2141.2008.07469.x

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：492 / 506

页数：15