1. microRNAome Expression in Chronic Lymphocytic Leukemia: Comparison with Normal B-cell Subsets and Correlations with Prognostic and Clinical Parameters
- Author
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Serena Matis, Cristian Bassi, Massimo Negrini, Sonia Fabris, Anna Grazia Recchia, Gian Matteo Rigolin, Manuela Ferracin, Monica Colombo, Antonino Neri, Barbara Zagatti, Lucilla D'Abundo, Giandomenico Russo, Fortunato Morabito, George A. Calin, Luca Agnelli, Manlio Ferrarini, Elena Saccenti, Sabrina Bossio, Daniele Reverberi, Marta Lionetti, Massimo Gentile, Pierfrancesco Tassone, Silvia Sabbioni, Giovanna Cutrona, 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 AG, Bossio S, Reverberi D, Rigolin G, Calin GA, Sabbioni S, Russo G, Tassone P, Morabito F, Ferrarini M, and Neri A.
- Subjects
Cancer Research ,tumor suppressor ,Immunoglobulin Heavy Chain ,Chronic lymphocytic leukemia ,B-Lymphocyte Subsets ,Trisomy ,Disease ,Biology ,medicine.disease_cause ,Chromosome Aberration ,survival ,NO ,immune system diseases ,hemic and lymphatic diseases ,microRNA ,CLL patients, profiling reveals, tumor suppressor, down regulation, 17p deletion, mir-34a, cancer, mir29, survival ,medicine ,Chromosomes, Human ,Humans ,cancer ,profiling reveals ,Cells, Cultured ,In Situ Hybridization, Fluorescence ,B cell ,B-Lymphocyte Subset ,Chromosome Aberrations ,mir-34a ,Mutation ,Cancer ,MicroRNA ,mir29 ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,17p deletion ,CLL patients ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,medicine.anatomical_structure ,Oncology ,Immunology ,Disease Progression ,Immunoglobulin Heavy Chains ,IGHV@ ,down regulation ,Human - 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 progression-free 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. Clin Cancer Res; 20(15); 4141–53. ©2014 AACR.
- Published
- 2014
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