title: Chromosome 2p gain in monoclonal B-cell lymphocytosis and in early stage chronic lymphocytic leukemia.
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.
authors.affiliation: Dipartimento di Scienze Cliniche e di Comunità, Università degli Studi di Milano e Ematologia 1 CTMO, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Fabris
authors.forename: Laura
authors.initials: L
authors.lastname: Mosca
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cutrona
authors.forename: Marta
authors.initials: M
authors.lastname: Lionetti
authors.forename: Luca
authors.initials: L
authors.lastname: Agnelli
authors.forename: Gabriella
authors.initials: G
authors.lastname: Ciceri
authors.forename: Marzia
authors.initials: M
authors.lastname: Barbieri
authors.forename: Francesco
authors.initials: F
authors.lastname: Maura
authors.forename: Serena
authors.initials: S
authors.lastname: Matis
authors.forename: Monica
authors.initials: M
authors.lastname: Colombo
authors.forename: Massimo
authors.initials: M
authors.lastname: Gentile
authors.forename: Anna Grazia
authors.initials: AG
authors.lastname: Recchia
authors.forename: Emanuela
authors.initials: E
authors.lastname: Anna Pesce
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Raimondo
authors.forename: Caterina
authors.initials: C
authors.lastname: Musolino
authors.forename: Marco
authors.initials: M
authors.lastname: Gobbi
authors.forename: Nicola
authors.initials: N
authors.lastname: Di Renzo
authors.forename: Francesca Romana
authors.initials: FR
authors.lastname: Mauro
authors.forename: Maura
authors.initials: M
authors.lastname: Brugiatelli
authors.forename: Fiorella
authors.initials: F
authors.lastname: Ilariucci
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Lipari
authors.forename: Francesco
authors.initials: F
authors.lastname: Angrilli
authors.forename: Ugo
authors.initials: U
authors.lastname: Consoli
authors.forename: Alberto
authors.initials: A
authors.lastname: Fragasso
authors.forename: Stefano
authors.initials: S
authors.lastname: Molica
authors.forename: Gianluca
authors.initials: G
authors.lastname: Festini
authors.forename: Iolanda
authors.initials: I
authors.lastname: Vincelli
authors.forename: Agostino
authors.initials: A
authors.lastname: Cortelezzi
authors.forename: Massimo
authors.initials: M
authors.lastname: Federico
authors.forename: Fortunato
authors.initials: F
authors.lastname: Morabito
authors.forename: Manlio
authors.initials: M
authors.lastname: Ferrarini
authors.forename: Antonino
authors.initials: A
authors.lastname: Neri
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics / Q000378:metabolism*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D008218:Lymphocytosis / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D015854:Up-Regulation / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins