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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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NEOPLASIA
Quantitative technologies establish a novel microRNA profile of chronic lymphocytic leukemia
Valerio Fulci1,
Sabina Chiaretti2,
Marina Goldoni1,
Gianluca Azzalin1,
Nicoletta Carucci1,
Simona Tavolaro2,
Leandro Castellano1,
Armando Magrelli1,
Franca Citarella1,
Monica Messina2,
Roberta Maggio2,
Nadia Peragine2,
Simona Santangelo2,
Francesca Romana Mauro2,
Pablo Landgraf3,
Thomas Tuschl3,
David B. Weir4,
Minchen Chien4,
James J. Russo4,
Jingyue Ju4,5,
Robert Sheridan6,
Chris Sander6,
Mihaela Zavolan7,
Anna Guarini2,
Robin Foà2, and
Giuseppe Macino1
1 Dipartimento di Biotecnologie Cellulari ed Ematologia, Sezione di Genetica Molecolare, Università di Roma "La Sapienza," Rome, Italy;
2 Dipartimento di Biotecnologie Cellulari ed Ematologia, Sezione di Ematologia, Università di Roma "La Sapienza," Rome, Italy;
3 Howard Hughes Medical Institute, Laboratory of RNA Molecular Biology, Rockefeller University, New York, NY;
4 Columbia Genome Center, New York, NY;
5 Department of Chemical Engineering, Columbia University, New York, NY;
6 Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, NY;
7 Biozentrum, Universität Basel, Switzerland
MicroRNAs (miRNAs) are a novel class of small noncoding RNAs that modulate the expression of genes at the posttranscriptional 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 2 independent and quantitative methods: miRNA cloning and quantitative real-time–polymerase chain reaction (qRT-PCR) of mature miRNAs. Both approaches show that miR-21 and miR-155 are dramatically overexpressed in patients with CLL, although the corresponding genomic loci are not amplified. miR-150 and miR-92 are also significantly deregulated in patients with CLL. 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 biologic 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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