REPRESSED BETA-1,3-GALACTOSYLTRANSFERASE IN THE TN SYNDROME

The human hematopoietic disorder named Tn syndrome has been ascribed t o an acquired stem cell mutation resulting in loss of beta-1,3-galacto syltransferase activity in affected Tn+ cells of the hematopoietic lin eages. 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 tr eatment of Tn+ T-lymphocytes from a patient (R.R.) afflicted with the Tn-syndrome with 5-azacytidine or Na n-butyrate resulted in re-express ion of the Thomsen-Friedenreich (TF) antigen, the product of beta-1,3- Gal-T activity [M. Thurnher, S. Rusconi, E.G. Berger, Persistent repre ssion of functional allele can be responsible for galactosyltransferas e deficiency in Tn syndrome, J. Clin. Invest. 91 (1993) 2103-2110]. To reduce these observations to a common pathogenetic mechanism responsi ble for the Tn-syndrome, more Tn patients need to be investigated. Her e, we describe similar Tn+ T-lymphocytes cultured ex vivo from patient M.Z. whose Tn+ syndrome was newly recognized. Tn+ and TF+ T-lymphocyt e cultures were characterized by flow cytometry and measurement of bet a-1,3-Gal-T and shown to be deficient in Tn+ cells. Furthermore, Tn+ c ells were treated with 5-azacytidine and Na n-butyrate as described be fore. Reoccurrence of beta-1,3-Gal-T activity dependent epitopes on th e 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. (C) 1998 Elsevier Science B.V.