title: Karyotype-specific microRNA signature in chronic lymphocytic leukemia.
abstract: 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.
authors.affiliation: Department of Molecular Virology, Immunology, and Medical Genetics and Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Rosa
authors.initials: R
authors.lastname: Visone
authors.forename: Laura Z
authors.initials: LZ
authors.lastname: Rassenti
authors.forename: Angelo
authors.initials: A
authors.lastname: Veronese
authors.forename: Cristian
authors.initials: C
authors.lastname: Taccioli
authors.forename: Stefan
authors.initials: S
authors.lastname: Costinean
authors.forename: Baltazar D
authors.initials: BD
authors.lastname: Aguda
authors.forename: Stefano
authors.initials: S
authors.lastname: Volinia
authors.forename: Manuela
authors.initials: M
authors.lastname: Ferracin
authors.forename: Jeff
authors.initials: J
authors.lastname: Palatini
authors.forename: Veronica
authors.initials: V
authors.lastname: Balatti
authors.forename: Hansjuerg
authors.initials: H
authors.lastname: Alder
authors.forename: Massimo
authors.initials: M
authors.lastname: Negrini
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Kipps
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Croce
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002872:Chromosome Deletion; D002877:Chromosomes, Human; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000378:metabolism; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D014314:Trisomy; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D007135:Immunoglobulin Variable Region; D035683:MicroRNAs; D012334:RNA, Neoplasm; D051746:ZAP-70 Protein-Tyrosine Kinase