Interferon system defects in malignant T-cells.
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.
Heyman
M
M
Radiumhemmet, Karolinska Hospital, Stockholm, Sweden.
Grandér
D
D
Bröndum-Nielsen
K
K
Cederblad
B
B
Liu
Y
Y
Xu
B
B
Einhorn
S
S
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis; D002455:Cell Division / Q000187:drug effects; D002869:Chromosome Aberrations / Q000235:genetics / Q000378:metabolism; D002872:Chromosome Deletion; D025063:Chromosome Disorders; D002899:Chromosomes, Human, Pair 9; D004790:Enzyme Induction; D006720:Homozygote; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis / Q000235:genetics*; D016899:Interferon-beta / Q000096:biosynthesis / Q000235:genetics*; D015458:Leukemia, T-Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D016898:Interferon-alpha; D012333:RNA, Messenger; D016899:Interferon-beta; D015088:2',5'-Oligoadenylate Synthetase