Repressed beta-1,3-galactosyltransferase in the Tn syndrome.
The human hematopoietic disorder named Tn syndrome has been ascribed to an acquired stem cell mutation resulting in loss of beta-1,3-galactosyltransferase activity in affected Tn+ cells of the hematopoietic lineages. Recently, we could demonstrate that this deficiency is due to a repression of a functional allele of the beta-1,3-Gal-T gene since treatment of Tn+ T-lymphocytes from a patient (R.R.) afflicted with the Tn-syndrome with 5-azacytidine or Na n-butyrate resulted in re-expression of the Thomsen-Friedenreich (TF) antigen, the product of beta-1,3-Gal-T activity [M. Thurnher, S. Rusconi, E.G. Berger. Persistent repression of functional allele can be responsible for galactosyltransferase deficiency in Tn syndrome. J. Clin. Invest. 91 (1993) 2103-2110]. To reduce these observations to a common pathogenetic mechanism responsible for the Tn-syndrome, more Tn patients need to be investigated. Here, we describe similar Tn+ T-lymphocytes cultured ex vivo from patient M.Z. whose Tn+ syndrome was newly recognized. Tn+ and TF+ T-lymphocyte cultures were characterized by flow cytometry and measurement of beta-1,3-Gal-T and shown to be deficient in Tn+ cells. Furthermore, Tn+ cells were treated with 5-azacytidine and Na n-butyrate as described before. Reoccurrence of beta-1,3-Gal-T activity dependent epitopes on the cell surface of Tn+ cells was shown by flow cytometry. These support the notion of beta-1,3-Gal-T gene repression as a common pathogenetic mechanism underlying the Tn-syndrome.
Felner
K M
KM
Institute of Physiology, University of Zurich, Switzerland.
Dinter
A
A
Cartron
J P
JP
Berger
E G
EG
D015295:Antigens, Tumor-Associated, Carbohydrate / Q000096:biosynthesis* / Q000235:genetics* / Q000276:immunology; D015415:Biomarkers; D005700:Galactosyltransferases / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic; D006402:Hematologic Diseases / Q000201:enzymology* / Q000235:genetics* / Q000276:immunology; D006801:Humans; D013577:Syndrome
D015295:Antigens, Tumor-Associated, Carbohydrate; D015415:Biomarkers; C040286:Tn antigen; C016467:Thomsen-Friedenreich antigen; D005700:Galactosyltransferases