PERSISTENT REPRESSION OF A FUNCTIONAL ALLELE CAN BE RESPONSIBLE FOR GALACTOSYLTRANSFERASE DEFICIENCY IN TN SYNDROME

A human hematopoietic disorder designated as Tn syndrome or permanent mixed-field polyagglutinability has been ascribed to a stem cell mutat ion leading to a specific deficiency of UDP-Gal:GalNAcalpha1-O-Ser/Thr 61-3 galactosyltransferase (beta3Gal-T) activity in affected cells. T o test for the possibility that an allele of the beta3Gal-T gene might be repressed instead of mutated, we have investigated whether 5-azacy tidine or sodium n-butyrate, both inducers of gene expression, would r eactivate expression of beta3Gal-T in cloned enzyme-deficient T cells derived from a patient affected by the Tn syndrome. Flow cytometry rev ealed that a single treatment induced de novo expression of the Thomse n-Friedenreich antigen (Galbeta1-3GalNAc-R), the product of beta3Gal-T activity. In addition, a sialylated epitope on CD43 (leukosialin), wh ich is present on normal but not on beta3Gal-T-deficient T cells, was also reexpressed. Although no beta3Gal-T activity was detectable in un treated Tn syndrome T cells, after exposure to 5-azaC, beta3Gal-T acti vity reached nearly normal values. Both agents failed to reactivate be ta3Gal-T in Jurkat T leukemic cells, which also lack beta3Gal-T activi ty. These data demonstrate that Tn syndrome T cells contain an intact beta3Gal-T gene copy and that the enzyme deficiency in this patient is due to a persistent and complete but reversible repression of a funct ional allele. In contrast, the cause of beta3Gal-T deficiency a ears t o be different in Jurkat T cells.