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

Cancer Res. 1998 Sep 1;58(17):3773-6.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Cell Division
  • Chromosomes, Human, Pair 11*
  • Chromosomes, Human, Pair 19*
  • DNA-Binding Proteins / physiology*
  • Histone-Lysine N-Methyltransferase
  • Humans
  • Leukemia, B-Cell / genetics*
  • Leukemia, B-Cell / pathology
  • Leukemia, B-Cell / therapy
  • Myeloid-Lymphoid Leukemia Protein
  • Oligonucleotides, Antisense / pharmacology*
  • Oligonucleotides, Antisense / therapeutic use
  • Proto-Oncogenes*
  • Recombinant Fusion Proteins / physiology*
  • Transcription Factors*
  • Translocation, Genetic*
  • Tumor Cells, Cultured

Substances

  • DNA-Binding Proteins
  • KMT2A protein, human
  • Oligonucleotides, Antisense
  • Recombinant Fusion Proteins
  • Transcription Factors
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase