Submitted June 20, 2007
Accepted December 12, 2007
MicroRNA expression profiling in classical Hodgkin lymphoma
Alfons Navarro, Anna Gaya, Antonio Martinez, Alvaro Urbano-Ispizua, Aina Pons, Olga Balague, Bernat Gel, Pau Abrisqueta, Armando Lopez-Guillermo, Rosa Artells, Emili Montserrat, and Mariano Monzo*
Department of Human Anatomy and Embryology, Laboratory of Molecular Oncology, Medical School, University of Barcelona, Barcelona, Spain
Department of Hematology, Institut d'Investigacions Biomediques August Pi i Sunyer, Hospital Clinic Barcelona, Barcelona, Spain
Hematopathology Section, Laboratory of Pathology, Institut d'Investigacions Biomediques August Pi i Sunyer, Hospital Clinic Barcelona, Barcelona, Spain
Department of Software, Technical University of Catalonia (UPC), Barcelona, Spain
* Corresponding author; email: mmonzo{at}ub.edu.
MicroRNAs (miRNAs) are negative regulators of gene expression that play an important role in hematopoiesis and tumorigenesis. We analyzed miRNA expression in classical Hodgkin lymphoma (cHL) and the influence of Epstein Barr virus (EBV) infection on the miRNA expression profiles. The expression of 157 miRNAs in lymph nodes from 49 cHL patients and 10 reactive lymph nodes (RLNs) was analyzed by real time PCR. Hierarchical clustering revealed three well-defined groups: nodular sclerosis cHL, mixed cellularity cHL, and RLNs. A distinctive signature of 25 miRNAs differentiated cHL from RLNs, and 36 miRNAs were differentially expressed in the nodular sclerosis and mixed cellularity subtypes. These results were validated in a set of 30 cHLs and five RLNs and in three cHL cell lines. mir-96, mir-128a and mir-128b were selectively downregulated in cHL with EBV. Our findings suggest that miRNAs play an important role in the biology of cHL and may be useful in developing therapies targeting miRNAs.
