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Blood, 1 June 2007, Vol. 109, No. 11, pp. 4944-4951.
Prepublished online as a Blood First Edition Paper on February 27, 2007; DOI 10.1182/blood-2006-12-062398.
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Submitted December 12, 2006
Accepted January 31, 2007
Quantitative technologies establish a novel microRNA profile of chronic lymphocytic leukemia
Valerio Fulci, Sabina Chiaretti, Marina Goldoni, Gianluca Azzalin, Nicoletta Carucci, Simona Tavolaro, Leandro Castellano, Armando Magrelli, Franca Citarella, Monica Messina, Roberta Maggio, Nadia Peragine, Simona Santangelo, Francesca Romana Mauro, Pablo Landgraf, Thomas Tuschl, David B Weir, Minchen Chien, James J Russo, Jingyue Ju, Robert Sheridan, Chris Sander, Mihaela Zavolan, Anna Guarini, Robin Foa, and Giuseppe Macino*
Dipartimento di Biotecnologie Cellulari ed Ematologia, Sezione di Genetica Molecolare, Universita di Roma "La Sapienza", Rome, Italy
Dipartimento di Biotecnologie Cellulari ed Ematologia, Sezione di Ematologia, Universita di Roma "La Sapienza", Rome, Italy
Howard Hughes Medical Institute, Laboratory of RNA Molecular Biology, The Rockefeller University, New York, NY, United States
Columbia Genome Center, New York, NY, United States
Dept of Chemical Engineering, Columbia University, New York, NY, United States
Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, NY, United States
Biozentrum, Universitat Basel, Basel, Switzerland
* Corresponding author; email: macino{at}bce.uniroma1.it.
MicroRNAs (miRNAs) are a novel class of small non-coding RNAs which modulate the expression of genes at the post-transcriptional level. These small molecules have been shown to be involved in cancer, apoptosis and cell metabolism. In the present study we provide an informative profile of the expression of miRNAs in primary chronic lymphocytic leukemia (CLL) cells using two independent and quantitative methods: miRNA cloning and qRT-PCR of mature miRNAs. Both approaches show that miR-21 and miR-155 are dramatically overexpressed in CLL patients, although the corresponding genomic loci are not amplified. miR-150 and miR-92 are also significantly deregulated in CLL patients. In addition, we detected a marked miR-15a and miR-16 decrease in about 11% of cases. Finally, we identified a set of miRNAs whose expression correlates with biological parameters of prognostic relevance, particularly with the mutational status of the IgVH genes. In summary, the results of this study offer for the first time a comprehensive and quantitative profile of miRNA expression in CLL and their healthy counterpart, suggesting that miRNAs could play a primary role in the disease itself.
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