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Blood, 29 October 2009, Vol. 114, No. 18, pp. 3872-3879.
Prepublished online as a Blood First Edition Paper on August 28, 2009; DOI 10.1182/blood-2009-06-229211.


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LYMPHOID NEOPLASIA

Karyotype-specific microRNA signature in chronic lymphocytic leukemia

Rosa Visone1, Laura Z. Rassenti2, Angelo Veronese1,3, Cristian Taccioli1, Stefan Costinean1, Baltazar D. Aguda4, Stefano Volinia1, Manuela Ferracin3, Jeff Palatini1, Veronica Balatti1, Hansjuerg Alder1, Massimo Negrini3, Thomas J. Kipps2, and Carlo M. Croce1

1 Department of Molecular Virology, Immunology, and Medical Genetics and Comprehensive Cancer Center, The Ohio State University, Columbus; 2 Department of Medicine, Moores Cancer Center, University of California at San Diego, La Jolla; 3 Dipartimento di Medicina Sperimentale e Diagnostica, Università di Ferrara, Ferrara, Italy; and 4 Mathematical Biosciences Institute, The Ohio State University, Columbus

Chromosomal abnormalities, immunoglobulin heavy chain variable–region (IGHV) gene mutation status, and {zeta}-associated protein 70 (ZAP-70) expression levels have independent prognostic relevance in chronic lymphocytic leukemia (CLL); however, their concordance is variable. Because deregulation of microRNAs has been linked to disease initiation and progression in CLL, we studied the value of the microRNAs as a signature for CLL patients with specific chromosomal abnormalities. We identified 32 microRNAs able to discriminate the 11q deletion, 17p deletion, trisomy 12, 13q deletion, and normal karyotype cytogenetic subgroups. The expression values of 9 among the 32 microRNAs (miR-151-3p, miR-34a, miR-29c, miR-29b, miR-155, miR-148a, miR-146a, miR-146b5p, and miR-640) were correlated with gene expression data from the same samples to assess their biologic impact on CLL. In this study we also found that IGHV unmutated, high expression of ZAP-70 protein, and low expression of the miR-223, miR-29c, miR-29b, and miR-181 family were strongly associated with disease progression in CLL cases harboring 17p deletion, whereas in those harboring trisomy 12 only high expression of the miR-181a, among the analyzed parameters, suggested more aggressive disease. Thus, the use of the microRNA-based classifications may yield clinically useful biomarkers of tumor behavior in CLL.


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