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Expression of mutated IGHV3-23 genes in chronic lymphocytic leukemia identifies a disease subset with peculiar clinical and biological features

Expression of mutated IGHV3-23 genes in chronic lymphocytic leukemia identifies a disease subset with peculiar clinical and biological features
Expression of mutated IGHV3-23 genes in chronic lymphocytic leukemia identifies a disease subset with peculiar clinical and biological features
Purpose: B-cell chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease whose outcome can be foreseen by investigating the mutational status of immunoglobulin heavy chain variable (IGHV) genes. Moreover, a different prognosis was reported for CLL expressing specific IGHV genes in the context or not of stereotyped B-cell receptors. Here we investigated novel associations between usage of specific IGHV genes and clinical features in CLL.

Experimental design: Among 1,426 CLL-specific IG-rearrangements, stereotyped B-cell receptor clusters never utilized the IGHV3-23 gene. Given this notion, this study was aimed at characterizing the IGHV3-23 gene in CLL, and identifying the properties of IGHV3-23-expressing CLL.

Results: IGHV3-23 was the second most frequently used (134 of 1,426) and usually mutated (M; 109 of 134) IGHV gene in our CLL series. In the vast majority of M IGHV3-23 sequences, the configuration of the 13 amino acids involved in superantigen recognition was consistent with superantigen binding. Clinically, M IGHV3-23 CLL had shorter time-to-treatment than other M non-IGHV3-23 CLL, and multivariate analyses selected IGHV3-23 gene usage, Rai staging, and chromosomal abnormalities as independent prognosticators for M CLL. Compared with M non-IGHV3-23 CLL, the gene expression profile of M IGHV3-23 CLL was deprived in genes, including the growth/tumor suppressor genes PDCD4, TIA1, and RASSF5, whose downregulation is under control of miR-15a and miR-16-1. Accordingly, relatively higher levels of miR-15a and miR-16-1 were found in M IGHV3-23 compared with M non-IGHV3-23 CLL.

Conclusions: Altogether, expression of the IGHV3-23 gene characterizes a CLL subset with distinct clinical and biological features.
CLL, IGHV3-23, microRNAs, prognosis
1078-0432
620-628
Bomben, Riccardo
2de7f588-50b7-43f6-8bb9-ec0a0896b8e5
Dal-Bo, Michele
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Benedetti, Dania
e46d5648-e944-431f-bc90-94c0da342133
Capello, Daniela
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Forconi, Francesco
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Marconi, Daniela
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Bertoni, Francesco
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Maffei, Rossana
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Laurenti, Luca
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Rossi, Davide
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Del Principe, Maria Ilaria
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Luciano, Fabrizio
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Sozzi, Elisa
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Cattarossi, Ilaria
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Zucchetto, Antonella
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Rossi, Francesca Maria
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Bulian, Pietro
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Zucca, Emanuele
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Nicoloso, Milena S.
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Degan, Massimo
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Marasca, Roberto
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Efremov, Dimitar G.
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Del Poeta, Giovanni
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Gaidano, Gianluca
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Gattei, Valter
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Bomben, Riccardo
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Dal-Bo, Michele
5428e25a-6b4b-48ff-b3d5-1828b03a9205
Benedetti, Dania
e46d5648-e944-431f-bc90-94c0da342133
Capello, Daniela
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Forconi, Francesco
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Marconi, Daniela
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Bertoni, Francesco
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Maffei, Rossana
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Laurenti, Luca
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Rossi, Davide
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Del Principe, Maria Ilaria
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Luciano, Fabrizio
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Sozzi, Elisa
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Cattarossi, Ilaria
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Zucchetto, Antonella
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Rossi, Francesca Maria
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Bulian, Pietro
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Zucca, Emanuele
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Nicoloso, Milena S.
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Degan, Massimo
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Marasca, Roberto
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Efremov, Dimitar G.
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Del Poeta, Giovanni
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Gaidano, Gianluca
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Gattei, Valter
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Bomben, Riccardo, Dal-Bo, Michele, Benedetti, Dania, Capello, Daniela, Forconi, Francesco, Marconi, Daniela, Bertoni, Francesco, Maffei, Rossana, Laurenti, Luca, Rossi, Davide, Del Principe, Maria Ilaria, Luciano, Fabrizio, Sozzi, Elisa, Cattarossi, Ilaria, Zucchetto, Antonella, Rossi, Francesca Maria, Bulian, Pietro, Zucca, Emanuele, Nicoloso, Milena S., Degan, Massimo, Marasca, Roberto, Efremov, Dimitar G., Del Poeta, Giovanni, Gaidano, Gianluca and Gattei, Valter (2010) Expression of mutated IGHV3-23 genes in chronic lymphocytic leukemia identifies a disease subset with peculiar clinical and biological features. Clinical Cancer Research, 16 (2), 620-628. (doi:10.1158/1078-0432.CCR-09-1638). (PMID:20068100)

Record type: Article

Abstract

Purpose: B-cell chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease whose outcome can be foreseen by investigating the mutational status of immunoglobulin heavy chain variable (IGHV) genes. Moreover, a different prognosis was reported for CLL expressing specific IGHV genes in the context or not of stereotyped B-cell receptors. Here we investigated novel associations between usage of specific IGHV genes and clinical features in CLL.

Experimental design: Among 1,426 CLL-specific IG-rearrangements, stereotyped B-cell receptor clusters never utilized the IGHV3-23 gene. Given this notion, this study was aimed at characterizing the IGHV3-23 gene in CLL, and identifying the properties of IGHV3-23-expressing CLL.

Results: IGHV3-23 was the second most frequently used (134 of 1,426) and usually mutated (M; 109 of 134) IGHV gene in our CLL series. In the vast majority of M IGHV3-23 sequences, the configuration of the 13 amino acids involved in superantigen recognition was consistent with superantigen binding. Clinically, M IGHV3-23 CLL had shorter time-to-treatment than other M non-IGHV3-23 CLL, and multivariate analyses selected IGHV3-23 gene usage, Rai staging, and chromosomal abnormalities as independent prognosticators for M CLL. Compared with M non-IGHV3-23 CLL, the gene expression profile of M IGHV3-23 CLL was deprived in genes, including the growth/tumor suppressor genes PDCD4, TIA1, and RASSF5, whose downregulation is under control of miR-15a and miR-16-1. Accordingly, relatively higher levels of miR-15a and miR-16-1 were found in M IGHV3-23 compared with M non-IGHV3-23 CLL.

Conclusions: Altogether, expression of the IGHV3-23 gene characterizes a CLL subset with distinct clinical and biological features.

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More information

e-pub ahead of print date: 12 January 2010
Published date: 15 January 2010
Keywords: CLL, IGHV3-23, microRNAs, prognosis
Organisations: Cancer Sciences

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Local EPrints ID: 358146
URI: https://eprints.soton.ac.uk/id/eprint/358146
ISSN: 1078-0432
PURE UUID: 4d0d0afb-505d-4ca3-a1ff-d86424f25222

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Date deposited: 08 Oct 2013 12:23
Last modified: 16 Jul 2019 21:21

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Contributors

Author: Riccardo Bomben
Author: Michele Dal-Bo
Author: Dania Benedetti
Author: Daniela Capello
Author: Daniela Marconi
Author: Francesco Bertoni
Author: Rossana Maffei
Author: Luca Laurenti
Author: Davide Rossi
Author: Maria Ilaria Del Principe
Author: Fabrizio Luciano
Author: Elisa Sozzi
Author: Ilaria Cattarossi
Author: Antonella Zucchetto
Author: Francesca Maria Rossi
Author: Pietro Bulian
Author: Emanuele Zucca
Author: Milena S. Nicoloso
Author: Massimo Degan
Author: Roberto Marasca
Author: Dimitar G. Efremov
Author: Giovanni Del Poeta
Author: Gianluca Gaidano
Author: Valter Gattei

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