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Blood, 15 August 2007, Vol. 110, No. 4, pp. 1301-1307.
Prepublished online as a Blood First Edition Paper on May 7, 2007; DOI 10.1182/blood-2006-12-064865.


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NEOPLASIA

Gene-expression analysis identifies novel RBL2/p130 target genes in endemic Burkitt lymphoma cell lines and primary tumors

Giulia De Falco1,2, Eleonora Leucci1, Dido Lenze3, Pier Paolo Piccaluga4, Pier Paolo Claudio2, Anna Onnis1, Giovanna Cerino1, Joshua Nyagol1,5, Walter Mwanda5, Cristiana Bellan1, Michael Hummel3, Stefano Pileri4, Piero Tosi1, Harald Stein3, Antonio Giordano1,2, and Lorenzo Leoncini1

1 Department of Human Pathology and Oncology, University of Siena, Italy; 2 Sbarro Institute for Cancer Research and Molecular Medicine Center of Biotechnology, Temple University, Philadelphia, PA; 3 Institute of Pathology, Campus Benjamin Franklin, University of Berlin, Berlin, Germany; 4 Institute of Hematology and Medical Oncology, L. and A. Seragnoli, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy; and 5 Department of Pathology, Kenyatta National Hospital, University of Nairobi, Nairobi, Kenya

Burkitt lymphoma (BL) is a B-cell tumor whose characteristic gene aberration is the translocation t(8;14), which determines c-myc overexpression. Several genetic and epigenetic alterations other than c-myc overexpression have also been described in BL. It has been demonstrated that the RBL2/p130 gene, a member of the retinoblastoma family (pRbs), is mutated in BL cell lines and primary tumors. The aim of this study was to investigate the biologic effect of RBL2/p130 in BL cells and its possible role in lymphomagenesis. Therefore, we reintroduced a functional RBL2/p130 in BL cell lines where this gene was mutated. Our results demonstrated that RBL2/p130-transfected cells regain growth control. This suggests that RBL2/p130 may control the expression of several genes, which may be important for cell growth and viability. Gene-expression analysis revealed a modulation of several genes, including CGRRF1, RGS1, BTG1, TIA1, and PCDHA2, upon RBL2/p130 reintroduction. We then monitored their expression in primary tumors of endemic BL as well, demonstrating that their expression resembled those of the BL cell lines. In conclusion, these data suggest that, as RBL2/p130 modulates the expression of target genes, which are important for cell growth and viability, its inactivation may be relevant for the occurrence of BL.


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