title: Persistent repression of a functional allele can be responsible for galactosyltransferase deficiency in Tn syndrome.
abstract: A human hematopoietic disorder designated as Tn syndrome or permanent mixed-field polyagglutinability has been ascribed to a stem cell mutation leading to a specific deficiency of UDP-Gal:GalNAc alpha 1-O-Ser/Thr beta 1-3 galactosyltransferase (beta 3 Gal-T) activity in affected cells. To test for the possibility that an allele of the beta 3Gal-T gene might be repressed instead of mutated, we have investigated whether 5-azacytidine or sodium n-butyrate, both inducers of gene expression, would reactivate expression of beta 3Gal-T in cloned enzyme-deficient T cells derived from a patient affected by the Tn syndrome. Flow cytometry revealed that a single treatment induced de novo expression of the Thomsen-Friedenreich antigen (Gal beta 1-3GalNAc-R), the product of beta 3Gal-T activity. In addition, a sialylated epitope on CD43 (leukosialin), which is present on normal but not on beta 3Gal-T-deficient T cells, was also reexpressed. Although no beta 3Gal-T activity was detectable in untreated Tn syndrome T cells, after exposure to 5-azaC,beta 3Gal-T activity reached nearly normal values. Both agents failed to reactivate beta 3Gal-T in Jurkat T leukemic cells, which also lack beta 3Gal-T activity. These data demonstrate that Tn syndrome T cells contain an intact beta 3Gal-T gene copy and that the enzyme deficiency in this patient is due to a persistent and complete but reversible repression of a functional allele. In contrast, the cause of beta 3Gal-T deficiency appears to be different in Jurkat T cells.
authors.affiliation: Institute of Physiology, University of Zurich, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Thurnher
authors.forename: S
authors.initials: S
authors.lastname: Rusconi
authors.forename: E G
authors.initials: EG
authors.lastname: Berger
mesh_terms: D000483:Alleles; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000235:genetics / Q000378:metabolism*; D001374:Azacitidine / Q000494:pharmacology; D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D002240:Carbohydrate Sequence; D002999:Clone Cells; D004794:Enzyme Repression; D005700:Galactosyltransferases / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D006402:Hematologic Diseases / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D013577:Syndrome; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D002087:Butyrates; C040286:Tn antigen; D020148:Butyric Acid; D005700:Galactosyltransferases; C076385:glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase; D001374:Azacitidine