Interferon system defects in malignant T-cells

Leukemia. 1994 Mar;8(3):425-34.

Abstract

Deletions of chromosome 9p21-22 occur in acute lymphocytic leukemia (ALL), melanoma and glioma. With some exceptions, these deletions include the alpha- and beta-interferon (IFN) genes. In this study, the frequency of alpha- and beta-IFN gene deletions was investigated in 17 T-cell lines, and losses of IFN genes were related to other aspects of the IFN system. Deletions of alpha-/beta-IFN genes were observed in 7/17 cell lines. In two cases the deletions were homozygous for both loci. In most cases aberrations of chromosome 9 were also apparent on cytogenetic analysis. An increased proportion (40% as compared to the expected 13%) of the remaining ten cell lines showed homozygosity for all five common polymorphic alpha-/beta-IFN markers, possibly implicating allelic deletion by loss of heterozygosity (LOH) in some of these clones. The cell lines showed a large variability in IFN production, IFN-alpha receptor number, susceptibility to IFN measured as induction of the enzyme 2',5' oligoadenylate synthetase and cell growth inhibition. No correlations between loss of IFN genes and IFN-producing capacity, or susceptibility to IFN, were found. Of the seven cell lines with a normal IFN-gene dosage and heterozygosity for the alpha- and beta-IFN genes, three had a deficiency in their IFN-producing capacity and one was also insensitive to growth inhibition by IFN. All IFN-producing cell lines predominantly produced beta-IFN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2',5'-Oligoadenylate Synthetase / biosynthesis
  • Cell Division / drug effects
  • Chromosome Aberrations / genetics
  • Chromosome Aberrations / metabolism
  • Chromosome Deletion*
  • Chromosome Disorders
  • Chromosomes, Human, Pair 9
  • Enzyme Induction
  • Homozygote
  • Humans
  • Interferon-alpha / biosynthesis
  • Interferon-alpha / genetics*
  • Interferon-beta / biosynthesis
  • Interferon-beta / genetics*
  • Leukemia, T-Cell / genetics*
  • Leukemia, T-Cell / metabolism
  • Leukemia, T-Cell / pathology
  • RNA, Messenger / biosynthesis
  • Tumor Cells, Cultured

Substances

  • Interferon-alpha
  • RNA, Messenger
  • Interferon-beta
  • 2',5'-Oligoadenylate Synthetase