Effects of anti-tal-1 oligodeoxynucleotides in T-ALL cell lines.

TY - JOUR

T1 - Effects of anti-tal-1 oligodeoxynucleotides in T-ALL cell lines.

AU - Anderegg, B

AU - Horstmann, Martin

AU - Kabisch, H

PY - 1997

Y1 - 1997

N2 - Rearrangement of the gene tal-1 leads to transcriptional dysregulation and contributes to the formation of childhood T-cell acute lymphoblastic 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 potential of two different strategies was investigated, one targeting the cell line specific SIL/tal-1 fusion region, the other using an ODN complementary to tal-1 sequence downstream of the region not affected by any of the known types of tal-1 rearrangement. With both approaches a single-dose application of 3 mumol of ODN led to a significant antiproliferative effect of a about 25-60% in two T-ALL cell lines characterized by the SIL/tal-1 fusion gene. Investigation of the tal-1 mRNA level by reverse transcription-polymerase chain reaction was in concordance with these results: In both cell lines clearly less of the tal-1-specific fragment was generated after incubation with the antisense ODN tal-1 common than in the control experiments with a mismatched ODN or no ODN at all. Neither the antiproliferation antisense effect nor the downregulation of the steady state tal-1 mRNA level was observed in control cell lines bearing wildtype tal-1.

AB - Rearrangement of the gene tal-1 leads to transcriptional dysregulation and contributes to the formation of childhood T-cell acute lymphoblastic 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 potential of two different strategies was investigated, one targeting the cell line specific SIL/tal-1 fusion region, the other using an ODN complementary to tal-1 sequence downstream of the region not affected by any of the known types of tal-1 rearrangement. With both approaches a single-dose application of 3 mumol of ODN led to a significant antiproliferative effect of a about 25-60% in two T-ALL cell lines characterized by the SIL/tal-1 fusion gene. Investigation of the tal-1 mRNA level by reverse transcription-polymerase chain reaction was in concordance with these results: In both cell lines clearly less of the tal-1-specific fragment was generated after incubation with the antisense ODN tal-1 common than in the control experiments with a mismatched ODN or no ODN at all. Neither the antiproliferation antisense effect nor the downregulation of the steady state tal-1 mRNA level was observed in control cell lines bearing wildtype tal-1.

M3 - SCORING: Zeitschriftenaufsatz

VL - 4

SP - 84

EP - 90

JO - CANCER GENE THER

JF - CANCER GENE THER

SN - 0929-1903

IS - 2

M1 - 2

ER -