Small nucleolar RNAs as new biomarkers in chronic lymphocytic leukemia

BMC Med Genomics. 2013 Sep 3:6:27. doi: 10.1186/1755-8794-6-27.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocyte Subsets / metabolism
  • Biomarkers, Tumor / genetics*
  • Cell Nucleus / genetics
  • Gene Expression Profiling*
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / diagnosis
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Neoplasm Staging
  • Prognosis
  • RNA, Small Nucleolar / genetics*
  • Risk
  • Transcription, Genetic

Substances

  • Biomarkers, Tumor
  • RNA, Small Nucleolar