TY - JOUR
T1 - LncRNA profiling in early-stage chronic lymphocytic leukemia identifies transcriptional fingerprints with relevance in clinical outcome
AU - Ronchetti, Domenica
AU - Manzoni, Martina
AU - Agnelli, Luca
AU - Vinci, C.
AU - Fabris, Sonia
AU - Cutrona, Giovanna
AU - Matis, Serena
AU - Colombo, Monica
AU - Galletti, Serena
AU - Taiana, Elisa
AU - Recchia, Anna Grazia
AU - Bossio, Sabrina
AU - Gentile, Massimo
AU - Musolino, Caterina
AU - Di Raimondo, Francesco
AU - Grilli, A.
AU - Bicciato, Silvio
AU - Cortelezzi, Agostino
AU - Tassone, Pierfrancesco
AU - Morabito, Fortunato
AU - Ferrarini, Manlio
AU - Neri, Antonino
PY - 2016
Y1 - 2016
N2 - Long non-coding RNAs (lncRNAs) represent a novel class of functional RNA molecules with an important emerging role in cancer. To elucidate their potential pathogenetic role in chronic lymphocytic leukemia (CLL), a biologically and clinically heterogeneous neoplasia, we investigated lncRNAs expression in a prospective series of 217 early-stage Binet A CLL patients and 26 different subpopulations of normal B-cells, through a custom annotation pipeline of microarray data. Our study identified a 24-lncRNAsignature specifically deregulated in CLL compared with the normal B-cell counterpart. Importantly, this classifier was validated on an independent data set of CLL samples. Belonging to the lncRNA signature characterizing distinct molecular CLL subgroups, we identified lncRNAs recurrently associated with adverse prognostic markers, such as unmutated IGHV status, CD38 expression, 11q and 17p deletions, and NOTCH1 mutations. In addition, correlation analyses predicted a putative lncRNAs interplay with genes and miRNAs expression. Finally, we generated a 2-lncRNA independent risk model, based on lnc-IRF2-3 and lnc-KIAA1755-4 expression, able to distinguish three different prognostic groups in our series of early-stage patients. Overall, our study provides an important resource for future studies on the functions of lncRNAs in CLL, and contributes to the discovery of novel molecular markers with clinical relevance associated with the disease.
AB - Long non-coding RNAs (lncRNAs) represent a novel class of functional RNA molecules with an important emerging role in cancer. To elucidate their potential pathogenetic role in chronic lymphocytic leukemia (CLL), a biologically and clinically heterogeneous neoplasia, we investigated lncRNAs expression in a prospective series of 217 early-stage Binet A CLL patients and 26 different subpopulations of normal B-cells, through a custom annotation pipeline of microarray data. Our study identified a 24-lncRNAsignature specifically deregulated in CLL compared with the normal B-cell counterpart. Importantly, this classifier was validated on an independent data set of CLL samples. Belonging to the lncRNA signature characterizing distinct molecular CLL subgroups, we identified lncRNAs recurrently associated with adverse prognostic markers, such as unmutated IGHV status, CD38 expression, 11q and 17p deletions, and NOTCH1 mutations. In addition, correlation analyses predicted a putative lncRNAs interplay with genes and miRNAs expression. Finally, we generated a 2-lncRNA independent risk model, based on lnc-IRF2-3 and lnc-KIAA1755-4 expression, able to distinguish three different prognostic groups in our series of early-stage patients. Overall, our study provides an important resource for future studies on the functions of lncRNAs in CLL, and contributes to the discovery of novel molecular markers with clinical relevance associated with the disease.
UR - http://www.scopus.com/inward/record.url?scp=84989909596&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84989909596&partnerID=8YFLogxK
U2 - 10.1038/bcj.2016.77
DO - 10.1038/bcj.2016.77
M3 - Article
VL - 6
JO - Blood Cancer Journal
JF - Blood Cancer Journal
SN - 2044-5385
IS - 9
M1 - e468
ER -