ANTISENSE OLIGONUCLEOTIDES SUPPRESS B-CELL LYMPHOMA GROWTH IN A SCID-HU MOUSE MODEL

The t(14;18) translocation is found in the majority follicular lymphom as and some high grade B-cell lymphomas. This is results in deregulati on of the BCL-2 gene and appears to play a role in oncogenesis. Variou s numbers of cells from a cell line derived spontaneously from a patie nt with B-cell lymphoma bearing the t(14;18) translocation and negativ e for the Epstein-Barr virus (EBV) were injected by IP, IV, and SC rou tes into SCID mice. The mice developed lymphoma bearing the t(14;18) t ranslocation with as few as 5 x 10(6) cells within 28 days. This was d etermined by histological examination. The higher the cell inoculation the more rapidly the lymphoma developed. Engraftment of the tumour ce lls was determined by PCR for the t(14;18) breakpoint region on periph eral blood samples and could be detected prior to development of overt lymphoma. Having established a lymphoma model the cells were treated with antisense oligonucleotides to the first open reading frame of the BCL-2 gene prior to inoculation of the SCID mice. Control treatments with sense and nonsense oligonucleotides was also performed. At 28 day s the sense, nonsense and untreated cell SCID mice had developed lymph oma, however, the antisense treated group failed to develop lymphoma. The findings demonstrate the modelling of B-cell lymphoma bearing the t(14;18) translocation and the ability to modify the lymphoma process with the use of antisense oligonucleotides to the BCL-2 gene. Reductio n of the BCL2 protein suppresses the oncogenic potential of these lymp homa cells confirming that it plays an essential role in the developme nt of malignancy.