Integrated <i>N</i>- and <i>O</i>-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...

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Autores principales:	Constantin Blöchl, Di Wang, Katarina Madunić, Guinevere S. M. Lageveen-Kammeijer, Christian G. Huber, Manfred Wuhrer, Tao Zhang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	PGC nano-LC-MS<sup>2</sup> <i>N</i>-glycosylation <i>O</i>-glycosylation tumor microenvironment sialyl Lewis x/a α-2,8 sialylation Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/dc376e97eb274358821249a8a8319228
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spelling	oai:doaj.org-article:dc376e97eb274358821249a8a83192282021-11-25T17:10:54ZIntegrated <i>N</i>- and <i>O</i>-Glycomics of Acute Myeloid Leukemia (AML) Cell Lines10.3390/cells101130582073-4409https://doaj.org/article/dc376e97eb274358821249a8a83192282021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3058https://doaj.org/toc/2073-4409Acute 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<sup>2</sup>), we qualitatively and quantitatively profiled <i>N</i>- and <i>O</i>-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.Constantin BlöchlDi WangKatarina MadunićGuinevere S. M. Lageveen-KammeijerChristian G. HuberManfred WuhrerTao ZhangMDPI AGarticlePGC nano-LC-MS<sup>2</sup><i>N</i>-glycosylation<i>O</i>-glycosylationtumor microenvironmentsialyl Lewis x/aα-2,8 sialylationBiology (General)QH301-705.5ENCells, Vol 10, Iss 3058, p 3058 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	PGC nano-LC-MS<sup>2</sup> <i>N</i>-glycosylation <i>O</i>-glycosylation tumor microenvironment sialyl Lewis x/a α-2,8 sialylation Biology (General) QH301-705.5
spellingShingle	PGC nano-LC-MS<sup>2</sup> <i>N</i>-glycosylation <i>O</i>-glycosylation tumor microenvironment sialyl Lewis x/a α-2,8 sialylation Biology (General) QH301-705.5 Constantin Blöchl Di Wang Katarina Madunić Guinevere S. M. Lageveen-Kammeijer Christian G. Huber Manfred Wuhrer Tao Zhang Integrated <i>N</i>- and <i>O</i>-Glycomics of Acute Myeloid Leukemia (AML) Cell Lines
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<sup>2</sup>), we qualitatively and quantitatively profiled <i>N</i>- and <i>O</i>-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	article
author	Constantin Blöchl Di Wang Katarina Madunić Guinevere S. M. Lageveen-Kammeijer Christian G. Huber Manfred Wuhrer Tao Zhang
author_facet	Constantin Blöchl Di Wang Katarina Madunić Guinevere S. M. Lageveen-Kammeijer Christian G. Huber Manfred Wuhrer Tao Zhang
author_sort	Constantin Blöchl
title	Integrated <i>N</i>- and <i>O</i>-Glycomics of Acute Myeloid Leukemia (AML) Cell Lines
title_short	Integrated <i>N</i>- and <i>O</i>-Glycomics of Acute Myeloid Leukemia (AML) Cell Lines
title_full	Integrated <i>N</i>- and <i>O</i>-Glycomics of Acute Myeloid Leukemia (AML) Cell Lines
title_fullStr	Integrated <i>N</i>- and <i>O</i>-Glycomics of Acute Myeloid Leukemia (AML) Cell Lines
title_full_unstemmed	Integrated <i>N</i>- and <i>O</i>-Glycomics of Acute Myeloid Leukemia (AML) Cell Lines
title_sort	integrated <i>n</i>- and <i>o</i>-glycomics of acute myeloid leukemia (aml) cell lines
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/dc376e97eb274358821249a8a8319228
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Integrated <i>N</i>- and <i>O</i>-Glycomics of Acute Myeloid Leukemia (AML) Cell Lines

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