LncRNA profiling in early-stage chronic lymphocytic leukemia identifies transcriptional fingerprints with relevance in clinical outcome

D. Ronchetti, M. Manzoni, L. Agnelli, C. Vinci, S. Fabris, G. Cutrona, S. Matis, M. Colombo, S. Galletti, E. Taiana, A. G. Recchia, S. Bossio, M. Gentile, C. Musolino, F. Di Raimondo, A. Grilli, S. Bicciato, A. Cortelezzi, P. Tassone, F. MorabitoM. Ferrarini, A. Neri

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article numbere468
JournalBlood Cancer Journal
Volume6
Issue number9
DOIs
Publication statusPublished - 2016

ASJC Scopus subject areas

  • Hematology
  • Oncology

Fingerprint Dive into the research topics of 'LncRNA profiling in early-stage chronic lymphocytic leukemia identifies transcriptional fingerprints with relevance in clinical outcome'. Together they form a unique fingerprint.

  • Cite this

    Ronchetti, D., Manzoni, M., Agnelli, L., Vinci, C., Fabris, S., Cutrona, G., Matis, S., Colombo, M., Galletti, S., Taiana, E., Recchia, A. G., Bossio, S., Gentile, M., Musolino, C., Di Raimondo, F., Grilli, A., Bicciato, S., Cortelezzi, A., Tassone, P., ... Neri, A. (2016). LncRNA profiling in early-stage chronic lymphocytic leukemia identifies transcriptional fingerprints with relevance in clinical outcome. Blood Cancer Journal, 6(9), [e468]. https://doi.org/10.1038/bcj.2016.77