Inhibition of Burkitt's lymphoma cells growth in SCID mice by a PNA specific for a regulatory sequence of the translocated c-myc

In Burkitt's lymphoma (BL) cells due to a t(8;14) chromosomal translocation c-myc is often placed in proximity to the Eμ enhancer of the Ig locus and upregulated. We demonstrated that in BL cells a peptide nucleic acid (PNA), complementary to intronic Eμ sequences (PNAEμwt), specifically blocks the expression of the c-myc oncogene under the Eμ enhancer control and inhibits BL cell growth in culture. Here, we investigated whether PNAEμwt was also able to block tumor growth in SCID mice inoculated with human BL cell lines. After subcutaneous inoculum in mice BL cells reproducibly form tumors. Both pre-treatment of BL cells with PNAEμwt before inoculum and chronic intravenous administration of PNAEμwt to mice already inoculated with BL cells selectively caused increased latency of tumor appearance and decreased final tumor size. Tumors from PNAEμwt-treated animals showed substantial areas of cell necrosis and of c-myc downregulation. Inhibition of tumor growth was specific and was not observed with PNAEμmut carrying sequence mutations and in BL cell lines where the translocated c-myc is not under the control of the Eμ enhancer. These data confirm the potential therapeutic value of PNA targeted to regulatory non-coding regions.