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 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.
Anderegg
B
B
Department of Hematology/Oncology, Children's Hospital, Clinical Center for the University of Hamburg, Germany. anderegg@uke.uni-hamburg.de
Horstmann
M
M
Kabisch
H
H
D051792:Basic Helix-Loop-Helix Proteins; D002455:Cell Division / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000493:pharmacokinetics / Q000494:pharmacology*; D015514:Oncogene Proteins, Fusion; D011506:Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000235:genetics; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016376:Oligonucleotides, Antisense; D015514:Oncogene Proteins, Fusion; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C071236:STIL protein, human; C067143:TAL1 protein, human