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Integrated N- and O-Glycomics of Acute Myeloid Leukemia (AML) Cell Lines
Acute myeloid leukemia (AML) is characterized by a dysregulated expansion of poorly differentiated myeloid cells. Although patients are usually treated effectively by chemotherapy, a high rate of relapsed or refractory disease poses a major hurdle in its treatment. Recently, several studies have pro...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616353/ https://www.ncbi.nlm.nih.gov/pubmed/34831278 http://dx.doi.org/10.3390/cells10113058 |
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author | Blöchl, Constantin Wang, Di Madunić, Katarina Lageveen-Kammeijer, Guinevere S. M. Huber, Christian G. Wuhrer, Manfred Zhang, Tao |
author_facet | Blöchl, Constantin Wang, Di Madunić, Katarina Lageveen-Kammeijer, Guinevere S. M. Huber, Christian G. Wuhrer, Manfred Zhang, Tao |
author_sort | Blöchl, Constantin |
collection | PubMed |
description | Acute myeloid leukemia (AML) is characterized by a dysregulated expansion of poorly differentiated myeloid cells. Although patients are usually treated effectively by chemotherapy, a high rate of relapsed or refractory disease poses a major hurdle in its treatment. Recently, several studies have proposed implications of protein glycosylation in the pathobiology of AML including chemoresistance. Accordingly, associations have been found between specific glycan epitopes and the outcome of the disease. To advance this poorly studied field, we performed an exploratory glycomics study characterizing 21 widely used AML cell lines. Exploiting the benefits of porous graphitized carbon chromatography coupled to tandem mass spectrometry (PGC nano-LC-MS(2)), we qualitatively and quantitatively profiled N- and O-linked glycans. AML cell lines exhibited distinct glycan fingerprints differing in relevant glycan traits correlating with their cellular phenotype as classified by the FAB system. By implementing transcriptomics data, specific glycosyltransferases and hematopoietic transcription factors were identified, which are candidate drivers of the glycan phenotype of these cells. In conclusion, we report the varying expression of glycan structures across a high number of AML cell lines, including those associated with poor prognosis, identified underlying glycosyltransferases and transcription factors, and provide insights into the regulation of the AML glycan repertoire. |
format | Online Article Text |
id | pubmed-8616353 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86163532021-11-26 Integrated N- and O-Glycomics of Acute Myeloid Leukemia (AML) Cell Lines Blöchl, Constantin Wang, Di Madunić, Katarina Lageveen-Kammeijer, Guinevere S. M. Huber, Christian G. Wuhrer, Manfred Zhang, Tao Cells Article Acute myeloid leukemia (AML) is characterized by a dysregulated expansion of poorly differentiated myeloid cells. Although patients are usually treated effectively by chemotherapy, a high rate of relapsed or refractory disease poses a major hurdle in its treatment. Recently, several studies have proposed implications of protein glycosylation in the pathobiology of AML including chemoresistance. Accordingly, associations have been found between specific glycan epitopes and the outcome of the disease. To advance this poorly studied field, we performed an exploratory glycomics study characterizing 21 widely used AML cell lines. Exploiting the benefits of porous graphitized carbon chromatography coupled to tandem mass spectrometry (PGC nano-LC-MS(2)), we qualitatively and quantitatively profiled N- and O-linked glycans. AML cell lines exhibited distinct glycan fingerprints differing in relevant glycan traits correlating with their cellular phenotype as classified by the FAB system. By implementing transcriptomics data, specific glycosyltransferases and hematopoietic transcription factors were identified, which are candidate drivers of the glycan phenotype of these cells. In conclusion, we report the varying expression of glycan structures across a high number of AML cell lines, including those associated with poor prognosis, identified underlying glycosyltransferases and transcription factors, and provide insights into the regulation of the AML glycan repertoire. MDPI 2021-11-06 /pmc/articles/PMC8616353/ /pubmed/34831278 http://dx.doi.org/10.3390/cells10113058 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Blöchl, Constantin Wang, Di Madunić, Katarina Lageveen-Kammeijer, Guinevere S. M. Huber, Christian G. Wuhrer, Manfred Zhang, Tao Integrated N- and O-Glycomics of Acute Myeloid Leukemia (AML) Cell Lines |
title | Integrated N- and O-Glycomics of Acute Myeloid Leukemia (AML) Cell Lines |
title_full | Integrated N- and O-Glycomics of Acute Myeloid Leukemia (AML) Cell Lines |
title_fullStr | Integrated N- and O-Glycomics of Acute Myeloid Leukemia (AML) Cell Lines |
title_full_unstemmed | Integrated N- and O-Glycomics of Acute Myeloid Leukemia (AML) Cell Lines |
title_short | Integrated N- and O-Glycomics of Acute Myeloid Leukemia (AML) Cell Lines |
title_sort | integrated n- and o-glycomics of acute myeloid leukemia (aml) cell lines |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616353/ https://www.ncbi.nlm.nih.gov/pubmed/34831278 http://dx.doi.org/10.3390/cells10113058 |
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