Tn polyagglutinability occurring in a patient with B cell lymphoma

Wallner, Maike; Waldner, R

doi:10.1007/bf00320046

Cited by 10 publications

(4 citation statements)

References 27 publications

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“…One mechanism for Tn antigen expression was found to be genetic mutations of Cosmc (6, 19, 20), or lossof-heterozygosity, in Cosmc (19). Our finding that Cosmc is epi-genetically silenced in Tn4 cells may be related to studies of Tn antigen expression in human leukemic cells, such as myeloma (44), lymphoma (45), and chronic lymphocytic leukemia (46). Aller et al (46) reported that the B cells from six of six patients with B-cell chronic lymphocytic leukemia were Tn-positive, whereas the blood cells from five normal individuals were negative for Tn expression.…”

Section: Discussionmentioning

confidence: 59%

Epigenetic Silencing of the Chaperone Cosmc in Human Leukocytes Expressing Tn Antigen

Song

Wang

et al. 2012

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 59%

Epigenetic Silencing of the Chaperone Cosmc in Human Leukocytes Expressing Tn Antigen

Song

Wang

et al. 2012

Journal of Biological Chemistry

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“…In patient R.R., 93% of erythrocytes were deficient in (33Gal-T activity. Exposed Tn antigen as a result of this deficiency is recognized by natural antibodies present in most human adult sera [38]. Moreover, Tnf cells may represent an additional antigenic stimulus that triggers the autoimmune response to Tn epitope-presenting cells resulting in hematologic abnormalities including mild hemolysis and moderate thrombopenia in patient R.R.…”

Section: Discussionmentioning

confidence: 99%

T cell clones with normal or defective O‐galactosylation from a patient with permanent mixed‐field polyagglutinability

et al. 1992

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To delineate the extent of O-galactosyltransferase deficiency within the lymphoid lineage, monoclonal antibody specific for the Thomsen-Friedenreich (TF) antigen (Gal beta 1----3GalNAc alpha 1-O-Ser/Thr) and its precursor the Tn antigen (GalNAc alpha 1-O-Ser/Thr) were applied to the flow cytometric analysis of peripheral blood lymphocytes from a patient with permanent mixed-field polyagglutinability (PMFP). We show that only a minor population of 4% expressed the Tn antigen which is in contrast to 93% of the patient's erythrocytes carrying the defect. Tn+ lymphocytes mainly belonged to the CD3+ subset, but were also CD19+ or CD16+. Both Tn+ and TF+ T cell clones from patient R. R. were established and shown to belong to the CD4+ or CD8+ antigenic subset. Three glycosyltransferase activities were determined in lysates from these clones: all Tn+ clones were deficient in UDP-Gal: GalNAc alpha 1-O-Ser/Thr beta 1----3 galactosyltransferase (beta 3Gal-T) activity; by contrast this activity was present in all lysates from TF-expressing clones. UDP-GalNAc: polypeptide alpha-N-acetylgalactosaminyltransferase (GalNAc-T) and UDP-Gal: GlcNAc-R beta 1----4 galactosyl-transferase (beta 4Gal-T) exhibited similar activities in both Tn+ and TF+ T cell clones. As a consequence of defective O-galactosylation in Tn+ T cells, cell surface sialic acid of Tn+ clones was reduced by greater than 50% when compared to TF+ clones as demonstrated by sialic acid-specific labeling using fluoresceinated Limax flavus agglutinin(LA) and flow cytometry. The Tn phenotype of T cell clones was stable for more than 1 year of continuous expansion in vitro. These data demonstrate that in PMFP, T cells may also be affected by the O-galactosyltransferase deficiency which is accompanied by a substantial loss of cell surface sialic acid. However, the frequency of Tn+ lymphocytes in peripheral blood from patient R.R. was strikingly low. These T cell clones should be useful to study the defect at a genetic level and the importance of O-linked carbohydrates for proper T cell function.

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“…These patients, who are also said to have blood group Tn (5), occasionally develop hemolytic anemia, thrombopenia, and leukopenia most likely mediated by anti-Tn natural antibodies present in normal serum (6). Tn polyagglutinability has been observed in the context of hemoproliferative disorders (7) and Tn antigen expression may also accompany malignant transformation (8). The enzyme deficiency was thought to arise from a somatic stem cell mutation resulting in the clonal penetration ofTn antigen-expressing cells into the various hematopoietic lineages (9).…”

Section: Introductionmentioning

confidence: 99%

Persistent repression of a functional allele can be responsible for galactosyltransferase deficiency in Tn syndrome.

Thurnher¹,

Rusconi²,

Berger³

1993

J. Clin. Invest.

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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:GalNAcal-O-Ser/Thr #1-3 galactosyltransferase (#3Gal-T) activity in affected cells. To test for the possibility that an allele of the ,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 #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,61-3GalNAc-R), the product of 63Gal-T activity. In addition, a sialylated epitope on CD43 (leukosialin), which is present on normal but not on ,3Gal-T-deficient T cells, was also reexpressed. Although no #3Gal-T activity was detectable in untreated Tn syndrome T cells, after exposure to 5-azaC, #3Gal-T activity reached nearly normal values. Both agents failed to reactivate ,63Gal-T in Jurkat T leukemic cells, which also lack #3Gal-T activity. These data demonstrate that Tn syndrome T cells contain an intact B83Gal-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 03Gal-T deficiency appears to be different in Jurkat T cells. (J. Clin.

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Tn polyagglutinability occurring in a patient with B cell lymphoma

Cited by 10 publications

References 27 publications

Epigenetic Silencing of the Chaperone Cosmc in Human Leukocytes Expressing Tn Antigen

Epigenetic Silencing of the Chaperone Cosmc in Human Leukocytes Expressing Tn Antigen

T cell clones with normal or defective O‐galactosylation from a patient with permanent mixed‐field polyagglutinability

Persistent repression of a functional allele can be responsible for galactosyltransferase deficiency in Tn syndrome.

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