title: microRNAome expression in chronic lymphocytic leukemia: comparison with normal B-cell subsets and correlations with prognostic and clinical parameters.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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 progression-free survival.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Dipartimento di Morfologia, Chirurgia e Medicina Sperimentale, Laboratorio per Tecnologie delle Terapie Avanzate, Tecnopolo, ngm@unife.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Negrini
authors.affiliation: IRCCS San Martino-IST, Genova;
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cutrona
authors.affiliation: Dipartimento di Morfologia, Chirurgia e Medicina Sperimentale.
authors.forename: Cristian
authors.initials: C
authors.lastname: Bassi
authors.affiliation: Dipartimento di Scienze Cliniche e di Comunità, Università di Milano and UOC Oncoematologia, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico Milano;
authors.forename: Sonia
authors.initials: S
authors.lastname: Fabris
authors.affiliation: Dipartimento di Morfologia, Chirurgia e Medicina Sperimentale.
authors.forename: Barbara
authors.initials: B
authors.lastname: Zagatti
authors.affiliation: IRCCS San Martino-IST, Genova;
authors.forename: Monica
authors.initials: M
authors.lastname: Colombo
authors.affiliation: Dipartimento di Morfologia, Chirurgia e Medicina Sperimentale, Laboratorio per Tecnologie delle Terapie Avanzate, Tecnopolo.
authors.forename: Manuela
authors.initials: M
authors.lastname: Ferracin
authors.affiliation: Dipartimento di Morfologia, Chirurgia e Medicina Sperimentale.
authors.forename: Lucilla
authors.initials: L
authors.lastname: D'Abundo
authors.affiliation: Sezione di Ematologia e Fisiopatologia dell'Emostasi, Azienda Università Ospedale di Ferrara, Ferrara;
authors.forename: Elena
authors.initials: E
authors.lastname: Saccenti
authors.affiliation: IRCCS San Martino-IST, Genova;
authors.forename: Serena
authors.initials: S
authors.lastname: Matis
authors.affiliation: Dipartimento di Scienze Cliniche e di Comunità, Università di Milano and UOC Oncoematologia, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico Milano;
authors.forename: Marta
authors.initials: M
authors.lastname: Lionetti
authors.affiliation: Dipartimento di Scienze Cliniche e di Comunità, Università di Milano and UOC Oncoematologia, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico Milano;
authors.forename: Luca
authors.initials: L
authors.lastname: Agnelli
authors.affiliation: Dipartimento di Oncoematologia, Azienda Ospedaliera di Cosenza;
authors.forename: Massimo
authors.initials: M
authors.lastname: Gentile
authors.affiliation: Dipartimento di Oncoematologia, Azienda Ospedaliera di Cosenza;
authors.forename: Anna Grazia
authors.initials: AG
authors.lastname: Recchia
authors.affiliation: Dipartimento di Oncoematologia, Azienda Ospedaliera di Cosenza;
authors.forename: Sabrina
authors.initials: S
authors.lastname: Bossio
authors.affiliation: IRCCS San Martino-IST, Genova;
authors.forename: Daniele
authors.initials: D
authors.lastname: Reverberi
authors.affiliation: Sezione di Ematologia e Fisiopatologia dell'Emostasi, Azienda Università Ospedale di Ferrara, Ferrara;
authors.forename: Gianmatteo
authors.initials: G
authors.lastname: Rigolin
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: George A
authors.initials: GA
authors.lastname: Calin
authors.affiliation: Dipartimento di Scienze della Vita e Biotecnologie, Università di Ferrara;
authors.forename: Silvia
authors.initials: S
authors.lastname: Sabbioni
authors.affiliation: Istituto Dermopatico dell'Immacolata-IRCCS, Roma;
authors.forename: Giandomenico
authors.initials: G
authors.lastname: Russo
authors.affiliation: Dipartimento di Medicina Sperimentale e Clinica, Magna Graecia University, Catanzaro, Italy; and.
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Tassone
authors.affiliation: Dipartimento di Oncoematologia, Azienda Ospedaliera di Cosenza;
authors.forename: Fortunato
authors.initials: F
authors.lastname: Morabito
authors.affiliation: IRCCS San Martino-IST, Genova;
authors.forename: Manlio
authors.initials: M
authors.lastname: Ferrarini
authors.affiliation: Dipartimento di Scienze Cliniche e di Comunità, Università di Milano and UOC Oncoematologia, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico Milano;
authors.forename: Antonino
authors.initials: A
authors.lastname: Neri
mesh_terms: D016175:B-Lymphocyte Subsets / Q000378:metabolism*; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000235:genetics; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D014314:Trisomy / Q000235:genetics
chemical_list: D007143:Immunoglobulin Heavy Chains; D035683:MicroRNAs