Antisense oligodeoxyribonucleotide against the MLL-LTG19 chimeric transcript inhibits cell growth and induces apoptosis in cells of an infantile leukemia cell line carrying the t(11;19) chromosomal translocation.
To clarify the role of the multiple lineage leukemia gene-leukemia translocation gene of chromosome 19 (MLL-LTG19) protein in leukemogenesis, we synthesized antisense oligodeoxyribonucleotide (ODN) against the fused region of the MLL-LTG19 chimeric transcript and treated KOCL33 cells carrying the t(11;19) translocation with antisense ODN. The antisense ODN inhibited cell growth and induced apoptosis in KOCL33 cells but not in Daudi cells, which have no t(11;19). The levels of MLL-LTG19 mRNA and MLL-LTG19 protein in KOCL33 cells treated with antisense ODN were shown to decrease with time by reverse transcription-PCR and Western blot analysis. These results suggest that the MLL-LTG19 fusion protein contributes to cell proliferation and malignant transformation in infantile acute leukemia cells carrying the t(11;19) translocation.
Akao
Y
Y
Gifu International Institute of Biotechnology, Mitake, Japan.
Mizoguchi
H
H
Misiura
K
K
Stec
W J
WJ
Seto
M
M
Ohishi
N
N
Yagi
K
K
D017209:Apoptosis; D002455:Cell Division; D002880:Chromosomes, Human, Pair 11; D002888:Chromosomes, Human, Pair 19; D004268:DNA-Binding Proteins / Q000502:physiology*; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D015448:Leukemia, B-Cell / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D051788:Myeloid-Lymphoid Leukemia Protein; D016376:Oligonucleotides, Antisense / Q000494:pharmacology* / Q000627:therapeutic use; D011519:Proto-Oncogenes; D011993:Recombinant Fusion Proteins / Q000502:physiology*; D014157:Transcription Factors; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D016376:Oligonucleotides, Antisense; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase