Quantitative technologies establish a novel microRNA profile of chronic lymphocytic leukemia

Author:

Fulci Valerio1,Chiaretti Sabina2,Goldoni Marina1,Azzalin Gianluca1,Carucci Nicoletta1,Tavolaro Simona2,Castellano Leandro1,Magrelli Armando1,Citarella Franca1,Messina Monica2,Maggio Roberta2,Peragine Nadia2,Santangelo Simona2,Mauro Francesca Romana2,Landgraf Pablo3,Tuschl Thomas3,Weir David B.4,Chien Minchen4,Russo James J.4,Ju Jingyue45,Sheridan Robert6,Sander Chris6,Zavolan Mihaela7,Guarini Anna2,Foà Robin2,Macino Giuseppe1

Affiliation:

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

Abstract

Abstract 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.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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