MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias.

Abstract

Little is known about the expression levels or function of micro-RNAs (miRNAs) in normal and neoplastic cells, although it is becoming clear that miRNAs play important roles in the regulation of gene expression during development [Ambros, V. (2003) Cell 113, 673-676; McManus, M. T. (2003) Semin. Cancer Biol. 13, 253-258]. We now report the genomewide expression profiling of miRNAs in human B cell chronic lymphocytic leukemia (CLL) by using a microarray containing hundreds of human precursor and mature miRNA oligonucleotide probes. This approach allowed us to identify significant differences in miRNome expression between CLL samples and normal CD5+ B cells; data were confirmed by Northern blot analyses and real-time RT-PCR. At least two distinct clusters of CLL samples can be identified that were associated with the presence or absence of Zap-70 expression, a predictor of early disease progression. Two miRNA signatures were associated with the presence or absence of mutations in the expressed Ig variableregion genes or with deletions at 13q14, respectively. These data suggest that miRNA expression patterns have relevance to the biological and clinical behavior of this leukemia.

• Authors: George Adrian Calin, Chang-Gong Liu, Cinzia Sevignani, Manuela Ferracin, Nadia Felli, Calin Dan Dumitru, Masayoshi Shimizu, Amelia Cimmino, Simona Zupo, Mariella Dono, Marie L Dell'Aquila, Hansjuerg Alder, Laura Rassenti, Thomas J Kipps, Florencia Bullrich, Massimo Negrini, Carlo M Croce
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 101 Issue 32 Pg. 11755-60 (Aug 10 2004) ISSN: 0027-8424 [Print] United States
• PMID: 15284443 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• MicroRNAs
• Oligonucleotide Probes
• RNA, Neoplasm
• Protein-Tyrosine Kinases
• ZAP-70 Protein-Tyrosine Kinase
• ZAP70 protein, human

Topics

• B-Lymphocytes
• Chromosome Deletion
• Chromosomes, Human, Pair 13
• Gene Expression Profiling (methods)
• Genes, Immunoglobulin
• Humans
• Leukemia, Lymphocytic, Chronic, B-Cell (genetics, pathology)
• MicroRNAs (analysis)
• Mutation
• Oligonucleotide Probes
• Polymerase Chain Reaction
• Prognosis
• Protein-Tyrosine Kinases (analysis, genetics)
• RNA, Neoplasm (analysis)
• ZAP-70 Protein-Tyrosine Kinase