دورية أكاديمية
N-linked glycosylation of the M-protein variable region: glycoproteogenomics reveals a new layer of personalized complexity in multiple myeloma.
| العنوان: | N-linked glycosylation of the M-protein variable region: glycoproteogenomics reveals a new layer of personalized complexity in multiple myeloma. |
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| المؤلفون: | Langerhorst P; Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands., Baerenfaenger M; Department of Neurology, Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands.; Division of BioAnalytical Chemistry, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands., Kulkarni P; Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.; Department of Medical BioSciences, Radboud University Medical Center, Nijmegen, The Netherlands.; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands., Nadal S; CY Cergy Paris Université, CNRS, BioCIS, Cergy-Pontoise, France., Wijnands C; Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands., Post MA; Department of Neurology, Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands., Noori S; Department of Neurology, Erasmus University Medical Center, Rotterdam, The Netherlands., vanDuijn MM; Department of Neurology, Erasmus University Medical Center, Rotterdam, The Netherlands., Joosten I; Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands., Dejoie T; Biochemistry Laboratory, Centre Hospitalier Universitaire (CHU), Nantes, France., van Gool AJ; Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands., Gloerich J; Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands., Lefeber DJ; Department of Neurology, Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands., Wessels HJCT; Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands., Jacobs JFM; Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. |
| المصدر: | Clinical chemistry and laboratory medicine [Clin Chem Lab Med] 2024 Feb 09; Vol. 62 (8), pp. 1626-1635. Date of Electronic Publication: 2024 Feb 09 (Print Publication: 2024). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Walter De Gruyter Country of Publication: Germany NLM ID: 9806306 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 1437-4331 (Electronic) Linking ISSN: 14346621 NLM ISO Abbreviation: Clin Chem Lab Med Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Berlin ; New York : Walter De Gruyter, c1998- |
| مواضيع طبية MeSH: | Multiple Myeloma*/metabolism , Multiple Myeloma*/genetics , Multiple Myeloma*/diagnosis, Humans ; Glycosylation ; Proteomics/methods ; Tandem Mass Spectrometry ; Glycoproteins/metabolism ; Chromatography, Liquid ; Myeloma Proteins/metabolism ; Myeloma Proteins/analysis |
| مستخلص: | Objectives: Multiple myeloma (MM) is a plasma cell malignancy characterized by a monoclonal expansion of plasma cells that secrete a characteristic M-protein. This M-protein is crucial for diagnosis and monitoring of MM in the blood of patients. Recent evidence has emerged suggesting that N-glycosylation of the M-protein variable (Fab) region contributes to M-protein pathogenicity, and that it is a risk factor for disease progression of plasma cell disorders. Current methodologies lack the specificity to provide a site-specific glycoprofile of the Fab regions of M-proteins. Here, we introduce a novel glycoproteogenomics method that allows detailed M-protein glycoprofiling by integrating patient specific Fab region sequences (genomics) with glycoprofiling by glycoproteomics. Methods: Glycoproteogenomics was used for the detailed analysis of de novo N-glycosylation sites of M-proteins. First, Genomic analysis of the M-protein variable region was used to identify de novo N-glycosylation sites. Subsequently glycopeptide analysis with LC-MS/MS was used for detailed analysis of the M-protein glycan sites. Results: Genomic analysis uncovered a more than two-fold increase in the Fab Light Chain N-glycosylation of M-proteins of patients with Multiple Myeloma compared to Fab Light Chain N-glycosylation of polyclonal antibodies from healthy individuals. Subsequent glycoproteogenomics analysis of 41 patients enrolled in the IFM 2009 clinical trial revealed that the majority of the Fab N-glycosylation sites were fully occupied with complex type glycans, distinguishable from Fc region glycans due to high levels of sialylation, fucosylation and bisecting structures. Conclusions: Together, glycoproteogenomics is a powerful tool to study de novo Fab N-glycosylation in plasma cell dyscrasias. (© 2024 the author(s), published by De Gruyter, Berlin/Boston.) |
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| فهرسة مساهمة: | Keywords: M-protein; N-glycosylation; glycoproteogenomics; multiple myeloma; variable region |
| المشرفين على المادة: | 0 (Glycoproteins) 0 (Myeloma Proteins) |
| تواريخ الأحداث: | Date Created: 20240209 Date Completed: 20240624 Latest Revision: 20240624 |
| رمز التحديث: | 20240624 |
| DOI: | 10.1515/cclm-2023-1189 |
| PMID: | 38332688 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1437-4331 |
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| DOI: | 10.1515/cclm-2023-1189 |