lncRNA profiling in early-stage chronic lymphocytic leukemia identifies transcriptional fingerprints with relevance in clinical outcome.
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-lncRNA-signature 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.
Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
D
D
Ronchetti
Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
M
M
Manzoni
Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
L
L
Agnelli
Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
C
0000-0001-5689-7169
C
Vinci
Hematology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
S
S
Fabris
Molecular Pathology Unit, IRCCS-A.O.U. San Martino-IST, Genoa, Italy.
G
G
Cutrona
Molecular Pathology Unit, IRCCS-A.O.U. San Martino-IST, Genoa, Italy.
S
S
Matis
Molecular Pathology Unit, IRCCS-A.O.U. San Martino-IST, Genoa, Italy.
M
M
Colombo
Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
S
S
Galletti
Hematology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
E
E
Taiana
Hematology Unit, Department of Onco-Hematology, A.O. of Cosenza, Cosenza, Italy.|Biotechnology Research Unit, Aprigliano, A.O./ASP of Cosenza, Cosenza, Italy.
A G
AG
Recchia
Hematology Unit, Department of Onco-Hematology, A.O. of Cosenza, Cosenza, Italy.|Biotechnology Research Unit, Aprigliano, A.O./ASP of Cosenza, Cosenza, Italy.
S
S
Bossio
Hematology Unit, Department of Onco-Hematology, A.O. of Cosenza, Cosenza, Italy.
M
M
Gentile
School and Division of Hematology, University Hospital 'G. Martino', Messina, Italy.
C
C
Musolino
Department of Biomedical Sciences, Division of Haematology, University of Catania and Ferrarotto Hospital, Catania, Italy.
F
F
Di Raimondo
Center for Genome Research Dept. of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
A
A
Grilli
Center for Genome Research Dept. of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
S
0000-0002-1944-7078
S
Bicciato
Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.|Hematology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
A
A
Cortelezzi
Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy.
P
P
Tassone
Hematology Unit, Department of Onco-Hematology, A.O. of Cosenza, Cosenza, Italy.|Biotechnology Research Unit, Aprigliano, A.O./ASP of Cosenza, Cosenza, Italy.
F
F
Morabito
Scientific Direction, IRCCS-A.O.U. San Martino-IST, Genoa, Italy.
M
M
Ferrarini
Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.|Hematology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
A
A
Neri
D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D016000:Cluster Analysis; D018450:Disease Progression; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D034622:RNA Interference; D062085:RNA, Long Noncoding; D059467:Transcriptome
D035683:MicroRNAs; D062085:RNA, Long Noncoding