1. ¹S.C. Oncologia Medica C, Istituto Nazionale per la Ricerca sul Cancro, IST, Genova, Italy
2. ²S.S. Sperimentazione su Modelli Animali, Istituto Nazionale per la Ricerca sul Cancro, IST, Genova, Italy
3. ³S.C. Oncologia Sperimentale F, Istituto Nazionale per la Ricerca sul Cancro, IST, Genova, Italy
4. ⁴DIMES, Biochemistry Section, and Center of Excellence for Biomedical Research, Università degli Studi di Genova, Genova, Italy
5. ⁵UO Anatomia ed Istologia Patologica, La Spezia, Italy
6. ⁶DOBIG, Biochemistry Section, and Center of Excellence for Biomedical Research, Università degli Studi di Genova, Genova, Italy

Correspondence: Dr L Boffa, Istituto Nazionale per la Ricerca sul Cancro, IST, Oncologia Medica C, L.go R. Benzi, 10, 16132 Genova, Italy. E-mail: lidia.boffa@istge.it

⁷These two authors contributed equally to this work.

Received 10 August 2008; Revised 3 February 2009; Accepted 16 March 2009; Published online 10 April 2009.

Abstract

In human Burkitt's Lymphoma (BL) BRG cells, a t(8;14) translocation, placing c-myc near the E enhancer of the H chain locus, causes tumor expansion. Earlier, we showed that a peptide nucleic acid complementary to the E sequence (PNAE), specifically inhibited the expression of translocated c-myc and impaired the growth of BRG cells-induced subcutaneous tumors in mice suffering from severe combined immunodeficiency (SCID). In this study, the therapeutic potential of PNAE was evaluated in a systemic mouse model. BRG-BL cells transfected with the luciferase gene were inoculated intravenously into SCID mice resulting in a preferential expansion, similar to the one of human adult patients, in the abdominal cavity, central nervous system and bone marrow. The mice were chronically injected intraperitoneally either with PNAE or with control PNA. The treatment was stopped when the control animals developed severe neurological symptoms. As detected both by inspection at necropsy and imaging, overall tumor growth in PNAE-treated mice decreased by >80%. Histological and immunohistochemical studies showed, only in PNAE-treated mice, a substantially reduced BL cell growth at the major sites of invasion and vast areas of necrosis in the lymphomatous tissues, with concomitant c-myc expression downregulation. Altogether, the data support the therapeutic potential of PNAE in human adult BL.