Open Access Research article

Small nucleolar RNAs as new biomarkers in chronic lymphocytic leukemia

Domenica Ronchetti1, Laura Mosca1, Giovanna Cutrona2, Giacomo Tuana3, Massimo Gentile4, Sonia Fabris1, Luca Agnelli13, Gabriella Ciceri1, Serena Matis5, Carlotta Massucco5, Monica Colombo5, Daniele Reverberi6, Anna Grazia Recchia4, Sabrina Bossio4, Massimo Negrini7, Pierfrancesco Tassone8, Fortunato Morabito4, Manlio Ferrarini5 and Antonino Neri13*

Author Affiliations

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

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BMC Medical Genomics 2013, 6:27  doi:10.1186/1755-8794-6-27

Published: 3 September 2013

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.