Chromosome 2p gain in monoclonal B-cell lymphocytosis and in early stage chronic lymphocytic leukemia

Sonia Fabris, Laura Mosca, Giovanna Cutrona, Marta Lionetti, Luca Agnelli, Gabriella Ciceri, Marzia Barbieri, Francesco Maura, Serena Matis, Monica Colombo, Massimo Gentile, Anna Grazia Recchia, Emanuela Anna Pesce, Francesco Di Raimondo, Caterina Musolino, Marco Gobbi, Nicola Di Renzo, Francesca Romana Mauro, Maura Brugiatelli, Fiorella IlariucciMaria Grazia Lipari, Francesco Angrilli, Ugo Consoli, Alberto Fragasso, Stefano Molica, Gianluca Festini, Iolanda Vincelli, Agostino Cortelezzi, Massimo Federico, Fortunato Morabito, Manlio Ferrarini, Antonino Neri

Research output: Contribution to journalArticle

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Abstract

Recent studies have described chromosome 2p gain as a recurrent lesion in chronic lymphocytic leukemia (CLL). We investigated the 2p gain and its relationship with common prognostic biomarkers in a prospective series of 69 clinical monoclonal B-cell lymphocytosis (cMBL) and 218 early stage (Binet A) CLL patients. The 2p gain was detected by FISH in 17 patients (6%, 16 CLL, and 1 cMBL) and further characterized by single nucleotide polymorphism-array. Overall, unfavorable cytogenetic deletions, i.e., del(11)(q23) and del(17)(p13) (P = 0.002), were significantly more frequent in 2p gain cases, as well as unmutated status of IGHV (P <1 × 10-4) and CD38 (P <1 × 10-4) and ZAP-70 positive expression (P = 0.003). Furthermore, 2p gain patients had significantly higher utilization of stereotyped B-cell receptors compared with 2p negative patients (P = 0.009), and the incidence of stereotyped subset #1 in 2p gain patients was significantly higher than that found in the remaining CLLs (P = 0.031). Transcriptional profiling analysis identified several genes significantly upregulated in 2p gain CLLs, most of which mapped to 2p. Among these, NCOA1 and ROCK2 are known for their involvement in tumor progression in several human cancers, whereas among those located in different chromosomes, CAV1 at 7q31.1 has been recently identified to play a critical role in CLL progression. Thus, 2p gain can be present since the early stages of the disease, particularly in those cases characterized by other poor prognosis markers. The finding of genes upregulated in the cells with 2p gain provides new insights to define the pathogenic role of this lesion.

Original languageEnglish
Pages (from-to)24-31
Number of pages8
JournalAmerican Journal of Hematology
Volume88
Issue number1
DOIs
Publication statusPublished - Jan 2013

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Lymphocytosis
B-Cell Chronic Lymphocytic Leukemia
B-Lymphocytes
Chromosomes
Cytogenetics
Genes
Single Nucleotide Polymorphism
Neoplasms
Biomarkers
Incidence

ASJC Scopus subject areas

  • Hematology

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Chromosome 2p gain in monoclonal B-cell lymphocytosis and in early stage chronic lymphocytic leukemia. / Fabris, Sonia; Mosca, Laura; Cutrona, Giovanna; Lionetti, Marta; Agnelli, Luca; Ciceri, Gabriella; Barbieri, Marzia; Maura, Francesco; Matis, Serena; Colombo, Monica; Gentile, Massimo; Recchia, Anna Grazia; Anna Pesce, Emanuela; Di Raimondo, Francesco; Musolino, Caterina; Gobbi, Marco; Di Renzo, Nicola; Mauro, Francesca Romana; Brugiatelli, Maura; Ilariucci, Fiorella; Lipari, Maria Grazia; Angrilli, Francesco; Consoli, Ugo; Fragasso, Alberto; Molica, Stefano; Festini, Gianluca; Vincelli, Iolanda; Cortelezzi, Agostino; Federico, Massimo; Morabito, Fortunato; Ferrarini, Manlio; Neri, Antonino.

In: American Journal of Hematology, Vol. 88, No. 1, 01.2013, p. 24-31.

Research output: Contribution to journalArticle

Fabris, S, Mosca, L, Cutrona, G, Lionetti, M, Agnelli, L, Ciceri, G, Barbieri, M, Maura, F, Matis, S, Colombo, M, Gentile, M, Recchia, AG, Anna Pesce, E, Di Raimondo, F, Musolino, C, Gobbi, M, Di Renzo, N, Mauro, FR, Brugiatelli, M, Ilariucci, F, Lipari, MG, Angrilli, F, Consoli, U, Fragasso, A, Molica, S, Festini, G, Vincelli, I, Cortelezzi, A, Federico, M, Morabito, F, Ferrarini, M & Neri, A 2013, 'Chromosome 2p gain in monoclonal B-cell lymphocytosis and in early stage chronic lymphocytic leukemia', American Journal of Hematology, vol. 88, no. 1, pp. 24-31. https://doi.org/10.1002/ajh.23340
Fabris, Sonia ; Mosca, Laura ; Cutrona, Giovanna ; Lionetti, Marta ; Agnelli, Luca ; Ciceri, Gabriella ; Barbieri, Marzia ; Maura, Francesco ; Matis, Serena ; Colombo, Monica ; Gentile, Massimo ; Recchia, Anna Grazia ; Anna Pesce, Emanuela ; Di Raimondo, Francesco ; Musolino, Caterina ; Gobbi, Marco ; Di Renzo, Nicola ; Mauro, Francesca Romana ; Brugiatelli, Maura ; Ilariucci, Fiorella ; Lipari, Maria Grazia ; Angrilli, Francesco ; Consoli, Ugo ; Fragasso, Alberto ; Molica, Stefano ; Festini, Gianluca ; Vincelli, Iolanda ; Cortelezzi, Agostino ; Federico, Massimo ; Morabito, Fortunato ; Ferrarini, Manlio ; Neri, Antonino. / Chromosome 2p gain in monoclonal B-cell lymphocytosis and in early stage chronic lymphocytic leukemia. In: American Journal of Hematology. 2013 ; Vol. 88, No. 1. pp. 24-31.
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abstract = "Recent studies have described chromosome 2p gain as a recurrent lesion in chronic lymphocytic leukemia (CLL). We investigated the 2p gain and its relationship with common prognostic biomarkers in a prospective series of 69 clinical monoclonal B-cell lymphocytosis (cMBL) and 218 early stage (Binet A) CLL patients. The 2p gain was detected by FISH in 17 patients (6{\%}, 16 CLL, and 1 cMBL) and further characterized by single nucleotide polymorphism-array. Overall, unfavorable cytogenetic deletions, i.e., del(11)(q23) and del(17)(p13) (P = 0.002), were significantly more frequent in 2p gain cases, as well as unmutated status of IGHV (P <1 × 10-4) and CD38 (P <1 × 10-4) and ZAP-70 positive expression (P = 0.003). Furthermore, 2p gain patients had significantly higher utilization of stereotyped B-cell receptors compared with 2p negative patients (P = 0.009), and the incidence of stereotyped subset #1 in 2p gain patients was significantly higher than that found in the remaining CLLs (P = 0.031). Transcriptional profiling analysis identified several genes significantly upregulated in 2p gain CLLs, most of which mapped to 2p. Among these, NCOA1 and ROCK2 are known for their involvement in tumor progression in several human cancers, whereas among those located in different chromosomes, CAV1 at 7q31.1 has been recently identified to play a critical role in CLL progression. Thus, 2p gain can be present since the early stages of the disease, particularly in those cases characterized by other poor prognosis markers. The finding of genes upregulated in the cells with 2p gain provides new insights to define the pathogenic role of this lesion.",
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AU - Fabris, Sonia

AU - Mosca, Laura

AU - Cutrona, Giovanna

AU - Lionetti, Marta

AU - Agnelli, Luca

AU - Ciceri, Gabriella

AU - Barbieri, Marzia

AU - Maura, Francesco

AU - Matis, Serena

AU - Colombo, Monica

AU - Gentile, Massimo

AU - Recchia, Anna Grazia

AU - Anna Pesce, Emanuela

AU - Di Raimondo, Francesco

AU - Musolino, Caterina

AU - Gobbi, Marco

AU - Di Renzo, Nicola

AU - Mauro, Francesca Romana

AU - Brugiatelli, Maura

AU - Ilariucci, Fiorella

AU - Lipari, Maria Grazia

AU - Angrilli, Francesco

AU - Consoli, Ugo

AU - Fragasso, Alberto

AU - Molica, Stefano

AU - Festini, Gianluca

AU - Vincelli, Iolanda

AU - Cortelezzi, Agostino

AU - Federico, Massimo

AU - Morabito, Fortunato

AU - Ferrarini, Manlio

AU - Neri, Antonino

PY - 2013/1

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