Small nucleolar RNAs as new biomarkers in chronic lymphocytic leukemia
1 Department of Clinical Sciences and Community Health, University of Milano, Milano, Italy
2 SS Molecular Diagnostics, IRCCS S, Martino-IST, Genova, Italy
3 Department of Clinical Sciences and Community Health, University of Milan, Hematology 1 CTMO, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, F. Sforza, 35-20122, Milano, Italy
4 U.O.C. di Ematologia, Azienda Ospedaliera di Cosenza, Cosenza, Italy
5 Scientific Direction, IRCCS S Martino-IST, Genova, Italy
6 Department of Pathology IRCCS S Martino-IST, Genova, Italy
7 Department of Experimental and Clinical Medicine, University of Ferrara, Ferrara, Italy
8 Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy
BMC Medical Genomics 2013, 6:27 doi:10.1186/1755-8794-6-27Published: 3 September 2013
Small nucleolar RNAs (snoRNAs) and small Cajal body-specific RNAs are non-coding RNAs involved in the maturation of other RNA molecules. Alterations of sno/scaRNA expression may play a role in cancerogenesis. This study elucidates the patterns of sno/scaRNA expression in 211 chronic lymphocytic leukemia (CLL) patients (Binet stage A) also in comparison with those of different normal B-cell subsets.
The patterns of sno/scaRNA expression in highly purified CD19+ B-cells of 211 CLL patients and in 18 normal B-cell samples - 6 from peripheral blood, and 12 from tonsils (4 germinal center, 2 marginal zone, 3 switched memory and 3 naïve B-cells) - were analyzed on the Affymetrix GeneChip® Human Gene 1.0 ST array.
CLLs display a sno/scaRNAs expression profile similar to normal memory, naïve and marginal-zone B-cells, with the exception of a few down-regulated transcripts (SNORA31, -6, -62, and -71C). Our analyses also suggest some heterogeneity in the pattern of sno/scaRNAs expression which is apparently unrelated to the major biological (ZAP-70 and CD38), molecular (IGHV mutation) and cytogenetic markers. Moreover, we found that SNORA70F was significantly down-regulated in poor prognostic subgroups and this phenomenon was associated with the down-regulation of its host gene COBLL1. Finally, we generated an independent model based on SNORA74A and SNORD116-18 expression, which appears to distinguish two different prognostic CLL groups.
These data extend the view of sno/scaRNAs deregulation in cancer and may contribute to discover novel biomarkers associated with the disease and potentially useful to predict the clinical outcome of early stage CLL patients.