MicroRNAome expression in chronic lymphocytic leukemia: Comparison with normal B-cell subsets and correlations with prognostic and clinical parameters

Massimo Negrini, Giovanna Cutrona, Cristian Bassi, Sonia Fabris, Barbara Zagatti, Monica Colombo, Manuela Ferracin, Lucilla D'Abundo, Elena Saccenti, Serena Matis, Marta Lionetti, Luca Agnelli, Massimo Gentile, Anna Grazia Recchia, Sabrina Bossio, Daniele Reverberi, Gianmatteo Rigolin, George A. Calin, Silvia Sabbioni, Giandomenico RussoPierfrancesco Tassone, Fortunato Morabito, Manlio Ferrarini, Antonino Neri

Research output: Contribution to journalArticle

Abstract

Purpose: Despite its indolent nature, chronic lymphocytic leukemia (CLL) remains an incurable disease. To establish the potential pathogenic role of miRNAs, the identification of deregulated miRNAs in CLL is crucial. Experimental Design: We analyzed the expression of 723 mature miRNAs in 217 early-stage CLL cases and in various different normal B-cell subpopulations from tonsils and peripheral blood. Results: Our analyses indicated that CLL cells exhibited a miRNA expression pattern that was most similar to the subsets of antigen-experienced and marginal zone-like B cells. These normal subpopulations were used as reference to identify differentially expressed miRNAs in comparison with CLL. Differences related to the expression of 25 miRNAs were found to be independent from IGHV mutation status or cytogenetic aberrations. These differences, confirmed in an independent validation set, led to a novel comprehensive description of miRNAs potentially involved in CLL. We also identified miRNAs whose expression was distinctive of cases with mutated versus unmutated IGHV genes or cases with 13q, 11q, and 17p deletions and trisomy 12. Finally, analysis of clinical data in relation to miRNA expression revealed that miR26a, miR532-3p, miR146-5p, and miR29c* were strongly associated with progressionfree survival. Conclusion: This study provides novel information on miRNAs expressed by CLL and normal B-cell subtypes, with implication on the cell of origin of CLL. In addition, our findings indicate a number of deregulated miRNAs in CLL, which may play a pathogenic role and promote disease progression. Collectively, this information can be used for developing miRNA-based therapeutic strategies in CLL.

Original languageEnglish
Pages (from-to)4141-4153
Number of pages13
JournalClinical Cancer Research
Volume20
Issue number15
DOIs
Publication statusPublished - Aug 1 2014

    Fingerprint

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Negrini, M., Cutrona, G., Bassi, C., Fabris, S., Zagatti, B., Colombo, M., Ferracin, M., D'Abundo, L., Saccenti, E., Matis, S., Lionetti, M., Agnelli, L., Gentile, M., Recchia, A. G., Bossio, S., Reverberi, D., Rigolin, G., Calin, G. A., Sabbioni, S., ... Neri, A. (2014). MicroRNAome expression in chronic lymphocytic leukemia: Comparison with normal B-cell subsets and correlations with prognostic and clinical parameters. Clinical Cancer Research, 20(15), 4141-4153. https://doi.org/10.1158/1078-0432.CCR-13-2497