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Association between molecular lesions and specific B-cell receptor subsets in chronic lymphocytic leukemia

Association between molecular lesions and specific B-cell receptor subsets in chronic lymphocytic leukemia
Association between molecular lesions and specific B-cell receptor subsets in chronic lymphocytic leukemia
Genetic lesions and B-cell receptor (BCR) signaling are both oncogenic drivers in chronic lymphocytic leukemia (CLL). However, scant data are available on preferential associations between specific genetic alterations and stereotyped BCR subsets. By analyzing 1419 cases, 2 CLL subsets (2 and 8) harboring stereotyped BCR are enriched in specific molecular alterations influencing disease course. SF3B1 mutations are the genetic hallmark of IGHV3-21-CLL belonging to subset 2 (52%) but are evenly represented in nonstereotyped IGHV3-21-CLL. Trisomy 12 (87%) and NOTCH1 mutations (62%) characterize IGHV4-39-CLL belonging to subset 8 but occur with the expected frequency in IGHV4-39-CLL with heterogeneous BCR. Clinically, co-occurrence of SF3B1 mutations and subset 2 BCR configuration prompts disease progression in IGHV3-21-CLL, whereas cooperation between NOTCH1 mutations, +12, and subset 8 BCR configuration invariably primes CLL transformation into Richter syndrome. These findings provide a proof of concept that specific stereotyped BCR may promote or select molecular lesions influencing outcome.
0006-4971
4902-4905
Rossi, Davide
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Spina, Valeria
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Bomben, Riccardo
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Rasi, Silvia
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Dal-Bo, Michele
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Bruscaggin, Alessio
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Rossi, Francesca Maria
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Monti, Sara
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Degan, Massimo
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Ciardullo, Carmela
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Serra, Roberto
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Zucchetto, Antonella
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Nomdedeu, Josep
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Bulian, Pietro
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Grossi, Alberto
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Zaja, Francesco
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Pozzato, Gabriele
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Laurenti, Luca
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Efremov, Dimitar G
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Di-Raimondo, Francesco
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Marasca, Roberto
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Forconi, Francesco
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Del Poeta, Giovanni
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Gaidano, Gianluca
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Gattei, Valter
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Rossi, Davide
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Spina, Valeria
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Bomben, Riccardo
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Rasi, Silvia
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Dal-Bo, Michele
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Bruscaggin, Alessio
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Rossi, Francesca Maria
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Monti, Sara
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Degan, Massimo
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Ciardullo, Carmela
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Serra, Roberto
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Zucchetto, Antonella
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Nomdedeu, Josep
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Bulian, Pietro
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Grossi, Alberto
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Zaja, Francesco
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Pozzato, Gabriele
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Laurenti, Luca
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Efremov, Dimitar G
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Di-Raimondo, Francesco
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Marasca, Roberto
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Forconi, Francesco
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Del Poeta, Giovanni
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Gaidano, Gianluca
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Gattei, Valter
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Rossi, Davide, Spina, Valeria, Bomben, Riccardo, Rasi, Silvia, Dal-Bo, Michele, Bruscaggin, Alessio, Rossi, Francesca Maria, Monti, Sara, Degan, Massimo, Ciardullo, Carmela, Serra, Roberto, Zucchetto, Antonella, Nomdedeu, Josep, Bulian, Pietro, Grossi, Alberto, Zaja, Francesco, Pozzato, Gabriele, Laurenti, Luca, Efremov, Dimitar G, Di-Raimondo, Francesco, Marasca, Roberto, Forconi, Francesco, Del Poeta, Giovanni, Gaidano, Gianluca and Gattei, Valter (2013) Association between molecular lesions and specific B-cell receptor subsets in chronic lymphocytic leukemia. Blood, 121 (24), 4902-4905. (doi:10.1182/blood-2013-02-486209). (PMID:23637131)

Record type: Article

Abstract

Genetic lesions and B-cell receptor (BCR) signaling are both oncogenic drivers in chronic lymphocytic leukemia (CLL). However, scant data are available on preferential associations between specific genetic alterations and stereotyped BCR subsets. By analyzing 1419 cases, 2 CLL subsets (2 and 8) harboring stereotyped BCR are enriched in specific molecular alterations influencing disease course. SF3B1 mutations are the genetic hallmark of IGHV3-21-CLL belonging to subset 2 (52%) but are evenly represented in nonstereotyped IGHV3-21-CLL. Trisomy 12 (87%) and NOTCH1 mutations (62%) characterize IGHV4-39-CLL belonging to subset 8 but occur with the expected frequency in IGHV4-39-CLL with heterogeneous BCR. Clinically, co-occurrence of SF3B1 mutations and subset 2 BCR configuration prompts disease progression in IGHV3-21-CLL, whereas cooperation between NOTCH1 mutations, +12, and subset 8 BCR configuration invariably primes CLL transformation into Richter syndrome. These findings provide a proof of concept that specific stereotyped BCR may promote or select molecular lesions influencing outcome.

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More information

e-pub ahead of print date: 1 May 2013
Published date: 13 June 2013
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 358100
URI: http://eprints.soton.ac.uk/id/eprint/358100
ISSN: 0006-4971
PURE UUID: cc3cbbb6-525e-48fa-8cff-1c11dc6c1de2
ORCID for Francesco Forconi: ORCID iD orcid.org/0000-0002-2211-1831

Catalogue record

Date deposited: 04 Oct 2013 09:05
Last modified: 15 Mar 2024 03:40

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Contributors

Author: Davide Rossi
Author: Valeria Spina
Author: Riccardo Bomben
Author: Silvia Rasi
Author: Michele Dal-Bo
Author: Alessio Bruscaggin
Author: Francesca Maria Rossi
Author: Sara Monti
Author: Massimo Degan
Author: Carmela Ciardullo
Author: Roberto Serra
Author: Antonella Zucchetto
Author: Josep Nomdedeu
Author: Pietro Bulian
Author: Alberto Grossi
Author: Francesco Zaja
Author: Gabriele Pozzato
Author: Luca Laurenti
Author: Dimitar G Efremov
Author: Francesco Di-Raimondo
Author: Roberto Marasca
Author: Giovanni Del Poeta
Author: Gianluca Gaidano
Author: Valter Gattei

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