GALNT11 as a new molecular marker in chronic lymphocytic leukemia |
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Authors: | M.G. Libisch,M. Casá s,ML. Chiribao,P. Moreno,A. Cayota,E. Osinaga,P. Oppezzo,C. Robello |
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Affiliation: | 1. Molecular Biology Unit, Institut Pasteur de Montevideo, Montevideo, Uruguay;2. Cancer Research, AstraZeneca R&D, Boston, USA;3. Biochemistry Department, School of Medicine, Universidad de la República, Montevideo, Uruguay;4. Recombinant Protein Unit, Institut Pasteur de Montevideo, Montevideo, Uruguay;5. Molecular Oncology Unit, Institut Pasteur de Montevideo, Montevideo, Uruguay;6. Immunology Department, School of Medicine, Universidad de la República, Montevideo, Uruguay;g Tumor Immunology and Glycobiology Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay |
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Abstract: | Aberrant mucin O-glycosylation often occurs in different cancers and is characterized by immature expression of simple mucin-type carbohydrates. At present, there are some controversial reports about the Tn antigen (GalNAcα-O-Ser/Thr) expression and there is a great lack of information about the [UDP-N-acetyl-α-d-galactosamine:polypeptide N-acetylgalactosaminyltransferase (GalNAc-Ts)] expression in chronic lymphocytic leukemia (CLL). To gain insight in these issues we evaluated the Tn antigen expression in CLL patient samples using two Tn binding proteins with different fine specificity. We also studied the expression from 14 GalNAc-Ts genes in CLL patients by RT-PCR. Our results have provided additional information about the expression level of the Tn antigen, suggesting that a low density of Tn residues is expressed in CLL cells. We also found that GALNT11 was expressed in CLL cells and normal T cell whereas little or no expression was found in normal B cells. Based on these results, GALNT11 expression was assessed by qPCR in a cohort of 50 CLL patients. We found significant over-expression of GALNT11 in 96% of B–CLL cells when compared to normal B cells. Moreover, we confirmed the expression of this enzyme at the protein level. Finally we found that GALNT11 expression was significantly associated with the mutational status of the immunoglobulin heavy chain variable region (IGHV), [?2(1) = 18.26; P < 0.0001], lipoprotein lipase expression [?2(1) = 13.72; P = 0.0002] and disease prognosis [?2(1) = 15.49; P < 0.0001]. Our evidence suggests that CLL patient samples harbor aberrant O-glycosylation highlighted by Tn antigen expression and that the over-expression of GALNT11 constitutes a new molecular marker for CLL. |
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Keywords: | aa, amino acid(s) bp, base pair BSA, bovine serum albumin CD19, cluster of differentiation 19 CD3, cluster of differentiation 3 cDNA, DNA complementary to RNA CLL, chronic lymphocytic leukemia FBS, fetal bovine serum GalNAc-Ts, UDP-N-acetyl-α-d-galactosamine:polypeptide N-acetylgalactosaminyltransferase GALNT11, Gene that encode GalNAc-T11 GAPDH, Glyceraldehyde 3-phosphate dehydrogenase Ig, immunoglobulin(s) IGHV, immunoglobulin heavy chain variable region IIF, indirect immunofluorescence LPL, lipoprotein lipase mAB, monoclonal Antibody MMLV, Moloney Murine Leukemia Virus Mut, mutated PAGE, PA-gel electrophoresis PB, peripheral blood PBMCs, peripheral blood mononuclear cells PBS, phosphate-buffered saline PCA, peptide competition assay qPCR, quantitative real time PCR REST, Relative Expression Software Tool SDS, sodium dodecyl sulfate UM, unmutated VVB4, isolectin B4 from Vicia villosa ZAP-70, zeta-associated protein 70 |
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