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Comprehensive characterization of IGHV3-21-expressing B-cell chronic lymphocytic leukemia: an Italian multicenter study

Comprehensive characterization of IGHV3-21-expressing B-cell chronic lymphocytic leukemia: an Italian multicenter study
Comprehensive characterization of IGHV3-21-expressing B-cell chronic lymphocytic leukemia: an Italian multicenter study
IGHV3-21-using chronic lymphocytic leukemia (CLL) is a distinct entity with restricted immunoglobulin gene features and poor prognosis and is more frequently encountered in Northern than Southern Europe. To further investigate this subset and its geographic distribution in the context of a country (Italy) with both continental and Mediterranean areas, 37 IGHV3-21 CLLs were collected out of 1076 cases enrolled by different institutions from Northern or Central Southern Italy. Of the 37 cases, 18 were identified as homologous (hom)HCDR3-IGHV3-21 CLLs and were found almost exclusively (16 of 18) in Northern Italy; in contrast, 19 nonhomHCDR3-IGHV3-21 cases were evenly distributed throughout Italy. Clinically, poor survivals were documented for IGHV3-21 CLLs as well as for subgroups of mutated and homHCDR3-IGHV3-21 CLLs. Negative prognosticators CD38, ZAP-70, CD49d, and CD79b were expressed at higher levels in homHCDR3 than nonhomHCDR3-IGHV3-21 cases. Differential gene expression profiling (GEP) of 13 IGHV3-21 versus 52 non-IGHV3-21 CLLs identified, among 122 best-correlated genes, TGFB2 and VIPR1 as down- and up-regulated in IGHV3-21 CLL cases, respectively. Moreover, GEP of 7 homHCDR3 versus 6 nonhomHCDR3-IGHV3-21 CLLs yielded 20 differentially expressed genes, with WNT-16 being that expressed at the highest levels in homHCDR3-IGHV3-21 CLLs. Altogether, IGHV3-21 CLLs, including those with homHCDR3, had a peculiar global phenotype in part explaining their worse clinical outcome.
0006-4971
2989-2998
Bomben, Riccardo
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Dal Bo, Michele
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Capello, Daniela
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Benedetti, Dania
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Marconi, Daniela
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Zucchetto, Antonella
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Forconi, Francesco
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Maffei, Rossana
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Ghia, Emanuela M
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Laurenti, Luca
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Bulian, Pietro
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Del Principe, Maria Ilaria
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Palermo, Giuseppe
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Thorsélius, Mia
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Degan, Massimo
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Campanini, Renato
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Guarini, Anna
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Del Poeta, Giovanni
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Rosenquist, Richard
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Efremov, Dimitar G
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Marasca, Roberto
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Foà, Robin
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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
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Capello, Daniela
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Benedetti, Dania
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Marconi, Daniela
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Zucchetto, Antonella
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Forconi, Francesco
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Maffei, Rossana
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Ghia, Emanuela M
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Laurenti, Luca
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Bulian, Pietro
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Del Principe, Maria Ilaria
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Palermo, Giuseppe
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Thorsélius, Mia
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Degan, Massimo
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Campanini, Renato
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Guarini, Anna
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Del Poeta, Giovanni
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Rosenquist, Richard
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Efremov, Dimitar G
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Marasca, Roberto
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Foà, Robin
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Gaidano, Gianluca
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Gattei, Valter
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Bomben, Riccardo, Dal Bo, Michele, Capello, Daniela, Benedetti, Dania, Marconi, Daniela, Zucchetto, Antonella, Forconi, Francesco, Maffei, Rossana, Ghia, Emanuela M, Laurenti, Luca, Bulian, Pietro, Del Principe, Maria Ilaria, Palermo, Giuseppe, Thorsélius, Mia, Degan, Massimo, Campanini, Renato, Guarini, Anna, Del Poeta, Giovanni, Rosenquist, Richard, Efremov, Dimitar G, Marasca, Roberto, Foà, Robin, Gaidano, Gianluca and Gattei, Valter (2007) Comprehensive characterization of IGHV3-21-expressing B-cell chronic lymphocytic leukemia: an Italian multicenter study. Blood, 109 (7), 2989-2998. (doi:10.1182/blood-2006-10-051110). (PMID:17148579)

Record type: Article

Abstract

IGHV3-21-using chronic lymphocytic leukemia (CLL) is a distinct entity with restricted immunoglobulin gene features and poor prognosis and is more frequently encountered in Northern than Southern Europe. To further investigate this subset and its geographic distribution in the context of a country (Italy) with both continental and Mediterranean areas, 37 IGHV3-21 CLLs were collected out of 1076 cases enrolled by different institutions from Northern or Central Southern Italy. Of the 37 cases, 18 were identified as homologous (hom)HCDR3-IGHV3-21 CLLs and were found almost exclusively (16 of 18) in Northern Italy; in contrast, 19 nonhomHCDR3-IGHV3-21 cases were evenly distributed throughout Italy. Clinically, poor survivals were documented for IGHV3-21 CLLs as well as for subgroups of mutated and homHCDR3-IGHV3-21 CLLs. Negative prognosticators CD38, ZAP-70, CD49d, and CD79b were expressed at higher levels in homHCDR3 than nonhomHCDR3-IGHV3-21 cases. Differential gene expression profiling (GEP) of 13 IGHV3-21 versus 52 non-IGHV3-21 CLLs identified, among 122 best-correlated genes, TGFB2 and VIPR1 as down- and up-regulated in IGHV3-21 CLL cases, respectively. Moreover, GEP of 7 homHCDR3 versus 6 nonhomHCDR3-IGHV3-21 CLLs yielded 20 differentially expressed genes, with WNT-16 being that expressed at the highest levels in homHCDR3-IGHV3-21 CLLs. Altogether, IGHV3-21 CLLs, including those with homHCDR3, had a peculiar global phenotype in part explaining their worse clinical outcome.

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e-pub ahead of print date: 5 December 2006
Published date: 1 April 2007
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 358165
URI: https://eprints.soton.ac.uk/id/eprint/358165
ISSN: 0006-4971
PURE UUID: 03647e88-dbae-4546-a4f3-25cd02955dd3

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Date deposited: 08 Oct 2013 13:16
Last modified: 16 Jul 2019 21:21

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Contributors

Author: Riccardo Bomben
Author: Michele Dal Bo
Author: Daniela Capello
Author: Dania Benedetti
Author: Daniela Marconi
Author: Antonella Zucchetto
Author: Rossana Maffei
Author: Emanuela M Ghia
Author: Luca Laurenti
Author: Pietro Bulian
Author: Maria Ilaria Del Principe
Author: Giuseppe Palermo
Author: Mia Thorsélius
Author: Massimo Degan
Author: Renato Campanini
Author: Anna Guarini
Author: Giovanni Del Poeta
Author: Richard Rosenquist
Author: Dimitar G Efremov
Author: Roberto Marasca
Author: Robin Foà
Author: Gianluca Gaidano
Author: Valter Gattei

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