EFFECTS OF ANTI-TAL-1 OLIGODEOXYNUCLEOTIDES IN T-ALL CELL-LINES

Rearrangement of the gene tal-1 leads to transcriptional dysregulation and contributes to the formation of childhood T-cell acute lymphoblas tic leukemia. Therefore, we tried to interfere with the transcription of the SIL/tal-1 fusion gene, the most common form of aberrant tal-1, by treatment with antisense oligodeoxynucleotides (ODNs). The potentia l of two different strategies was investigated, one targeting the cell line specific SIL/tal-1 fusion region, the other using an ODN complem entary to a tal-1 sequence downstream of the region not affected by an y of the known types of tal-1 rearrangement. With both approaches a si ngle-dose application of 3 mu mol of ODN led to a significant antiprol iferative effect of about 25-60% in two T-ALL cell lines characterized by the SIL/tal-1 fusion gene. Investigation of the tal-1 mRNA level b y reverse transcription-polymerase chain reaction was in concordance w ith these results: In both cell lines clearly less of the tal-1-specif ic fragment was generated after incubation with the antisense ODN tal- 1 common than in the control experiments with a mismatched ODN or no O DN at all. Neither the antiproliferational antisense effect nor the do wnregulation of the steady state tal-1 mRNA level was observed in cont rol cell lines bearing wildtype tal-1.