Glycosphingolipid-Glycan Signatures of Acute Myeloid Leukemia Cell Lines Reflect Hematopoietic Differentiation

Di Wang; Tao Zhang; Katarina Madunic; Antonius A. de Waard; Constantin Blochl; Oleg A. Mayboroda; Marieke Griffioen; Robbert M. Spaapen; Christian G. Huber; Guinevere S. M. Lageveen-Kammeijer; Manfred Wuhrer

doi:10.1021/acs.jproteome.1c00911

Glycosphingolipid-Glycan Signatures of Acute Myeloid Leukemia Cell Lines Reflect Hematopoietic Differentiation

Di Wang, Tao Zhang, Katarina Madunic, Antonius A. de Waard, Constantin Blochl, Oleg A. Mayboroda, Marieke Griffioen, Robbert M. Spaapen, Christian G. Huber, Guinevere S. M. Lageveen-Kammeijer, Manfred Wuhrer^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

10 Citations (Scopus)

Abstract

Aberrant expression of certain glycosphingolipids (GSLs) is associated withthe differentiation of acute myeloid leukemia (AML) cells. However, the expressionpatterns of GSLs in AML are still poorly explored because of their complexity, the presenceof multiple isomeric structures, and tedious analytical procedures. In this study, weperformed an in-depth GSL glycan analysis of 19 AML cell lines using porous graphitizedcarbon liquid chromatography-mass spectrometry revealing strikingly different GSL glycanprofiles between the various AML cell lines. The cell lines of the M6 subtype showed a highexpression of gangliosides with alpha 2,3-sialylation and Neu5Gc, while the M2 and M5subtypes were characterized by high expression of (neo)lacto-series glycans and Lewis A/Xantigens. Integrated analysis of glycomics and available transcriptomics data revealed theassociation of GSL glycan abundances with the transcriptomics expression of certainglycosyltransferases (GTs) and transcription factors (TFs). In addition, correlations werefound between specific GTs and TFs. Our data reveal TFsGATA2,GATA1, andRUNX1as candidate inducers of the expression of gangliosides and sialylation via regulation of the GTsST3GAL2andST8SIA1.Inconclusion, we show that GSL glycan expression levels are associated with hematopoietic AML classifications and TF and GT geneexpression. Further research is needed to dissect the regulation of GSL expression and its role in hematopoiesis and associated malignancies

Original language	English
Pages (from-to)	1029-1040
Number of pages	12
Journal	Journal of Proteome Research
Volume	21
Issue number	4
DOIs	https://doi.org/10.1021/acs.jproteome.1c00911
Publication status	Published - 1-Apr-2022
Externally published	Yes

Keywords

glycosphingolipids
acute myeloid leukemia
glycosyltransferases
hematopoietic transcription factors
mass spectrometry
porous graphitized carbon liquid chromatography
N-GLYCOLYLNEURAMINIC ACID
GANGLIOSIDE GM3
SIALIC-ACID
EXPRESSION
FUCOSYLATION
ASSOCIATION
BIOLOGY
ISOMERS
TISSUE
GENE

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Wang, D., Zhang, T., Madunic, K., de Waard, A. A., Blochl, C., Mayboroda, O. A., Griffioen, M., Spaapen, R. M., Huber, C. G., Lageveen-Kammeijer, G. S. M., & Wuhrer, M. (2022). Glycosphingolipid-Glycan Signatures of Acute Myeloid Leukemia Cell Lines Reflect Hematopoietic Differentiation. Journal of Proteome Research, 21(4), 1029-1040. https://doi.org/10.1021/acs.jproteome.1c00911

@article{3d59c59cc99c49a1ad6fa3d9d5477715,

title = "Glycosphingolipid-Glycan Signatures of Acute Myeloid Leukemia Cell Lines Reflect Hematopoietic Differentiation",

abstract = "Aberrant expression of certain glycosphingolipids (GSLs) is associated withthe differentiation of acute myeloid leukemia (AML) cells. However, the expressionpatterns of GSLs in AML are still poorly explored because of their complexity, the presenceof multiple isomeric structures, and tedious analytical procedures. In this study, weperformed an in-depth GSL glycan analysis of 19 AML cell lines using porous graphitizedcarbon liquid chromatography-mass spectrometry revealing strikingly different GSL glycanprofiles between the various AML cell lines. The cell lines of the M6 subtype showed a highexpression of gangliosides with alpha 2,3-sialylation and Neu5Gc, while the M2 and M5subtypes were characterized by high expression of (neo)lacto-series glycans and Lewis A/Xantigens. Integrated analysis of glycomics and available transcriptomics data revealed theassociation of GSL glycan abundances with the transcriptomics expression of certainglycosyltransferases (GTs) and transcription factors (TFs). In addition, correlations werefound between specific GTs and TFs. Our data reveal TFsGATA2,GATA1, andRUNX1as candidate inducers of the expression of gangliosides and sialylation via regulation of the GTsST3GAL2andST8SIA1.Inconclusion, we show that GSL glycan expression levels are associated with hematopoietic AML classifications and TF and GT geneexpression. Further research is needed to dissect the regulation of GSL expression and its role in hematopoiesis and associated malignancies",

keywords = "glycosphingolipids, acute myeloid leukemia, glycosyltransferases, hematopoietic transcription factors, mass spectrometry, porous graphitized carbon liquid chromatography, N-GLYCOLYLNEURAMINIC ACID, GANGLIOSIDE GM3, SIALIC-ACID, EXPRESSION, FUCOSYLATION, ASSOCIATION, BIOLOGY, ISOMERS, TISSUE, GENE",

author = "Di Wang and Tao Zhang and Katarina Madunic and {de Waard}, {Antonius A.} and Constantin Blochl and Mayboroda, {Oleg A.} and Marieke Griffioen and Spaapen, {Robbert M.} and Huber, {Christian G.} and Lageveen-Kammeijer, {Guinevere S. M.} and Manfred Wuhrer",

year = "2022",

month = apr,

day = "1",

doi = "10.1021/acs.jproteome.1c00911",

language = "English",

volume = "21",

pages = "1029--1040",

journal = "Journal of Proteome Research",

issn = "1535-3893",

publisher = "NLM (Medline)",

number = "4",

}

Wang, D, Zhang, T, Madunic, K, de Waard, AA, Blochl, C, Mayboroda, OA, Griffioen, M, Spaapen, RM, Huber, CG, Lageveen-Kammeijer, GSM & Wuhrer, M 2022, 'Glycosphingolipid-Glycan Signatures of Acute Myeloid Leukemia Cell Lines Reflect Hematopoietic Differentiation', Journal of Proteome Research, vol. 21, no. 4, pp. 1029-1040. https://doi.org/10.1021/acs.jproteome.1c00911

TY - JOUR

T1 - Glycosphingolipid-Glycan Signatures of Acute Myeloid Leukemia Cell Lines Reflect Hematopoietic Differentiation

AU - Wang, Di

AU - Zhang, Tao

AU - Madunic, Katarina

AU - de Waard, Antonius A.

AU - Blochl, Constantin

AU - Mayboroda, Oleg A.

AU - Griffioen, Marieke

AU - Spaapen, Robbert M.

AU - Huber, Christian G.

AU - Lageveen-Kammeijer, Guinevere S. M.

AU - Wuhrer, Manfred

PY - 2022/4/1

Y1 - 2022/4/1

N2 - Aberrant expression of certain glycosphingolipids (GSLs) is associated withthe differentiation of acute myeloid leukemia (AML) cells. However, the expressionpatterns of GSLs in AML are still poorly explored because of their complexity, the presenceof multiple isomeric structures, and tedious analytical procedures. In this study, weperformed an in-depth GSL glycan analysis of 19 AML cell lines using porous graphitizedcarbon liquid chromatography-mass spectrometry revealing strikingly different GSL glycanprofiles between the various AML cell lines. The cell lines of the M6 subtype showed a highexpression of gangliosides with alpha 2,3-sialylation and Neu5Gc, while the M2 and M5subtypes were characterized by high expression of (neo)lacto-series glycans and Lewis A/Xantigens. Integrated analysis of glycomics and available transcriptomics data revealed theassociation of GSL glycan abundances with the transcriptomics expression of certainglycosyltransferases (GTs) and transcription factors (TFs). In addition, correlations werefound between specific GTs and TFs. Our data reveal TFsGATA2,GATA1, andRUNX1as candidate inducers of the expression of gangliosides and sialylation via regulation of the GTsST3GAL2andST8SIA1.Inconclusion, we show that GSL glycan expression levels are associated with hematopoietic AML classifications and TF and GT geneexpression. Further research is needed to dissect the regulation of GSL expression and its role in hematopoiesis and associated malignancies

AB - Aberrant expression of certain glycosphingolipids (GSLs) is associated withthe differentiation of acute myeloid leukemia (AML) cells. However, the expressionpatterns of GSLs in AML are still poorly explored because of their complexity, the presenceof multiple isomeric structures, and tedious analytical procedures. In this study, weperformed an in-depth GSL glycan analysis of 19 AML cell lines using porous graphitizedcarbon liquid chromatography-mass spectrometry revealing strikingly different GSL glycanprofiles between the various AML cell lines. The cell lines of the M6 subtype showed a highexpression of gangliosides with alpha 2,3-sialylation and Neu5Gc, while the M2 and M5subtypes were characterized by high expression of (neo)lacto-series glycans and Lewis A/Xantigens. Integrated analysis of glycomics and available transcriptomics data revealed theassociation of GSL glycan abundances with the transcriptomics expression of certainglycosyltransferases (GTs) and transcription factors (TFs). In addition, correlations werefound between specific GTs and TFs. Our data reveal TFsGATA2,GATA1, andRUNX1as candidate inducers of the expression of gangliosides and sialylation via regulation of the GTsST3GAL2andST8SIA1.Inconclusion, we show that GSL glycan expression levels are associated with hematopoietic AML classifications and TF and GT geneexpression. Further research is needed to dissect the regulation of GSL expression and its role in hematopoiesis and associated malignancies

KW - glycosphingolipids

KW - acute myeloid leukemia

KW - glycosyltransferases

KW - hematopoietic transcription factors

KW - mass spectrometry

KW - porous graphitized carbon liquid chromatography

KW - N-GLYCOLYLNEURAMINIC ACID

KW - GANGLIOSIDE GM3

KW - SIALIC-ACID

KW - EXPRESSION

KW - FUCOSYLATION

KW - ASSOCIATION

KW - BIOLOGY

KW - ISOMERS

KW - TISSUE

KW - GENE

U2 - 10.1021/acs.jproteome.1c00911

DO - 10.1021/acs.jproteome.1c00911

M3 - Article

SN - 1535-3893

VL - 21

SP - 1029

EP - 1040

JO - Journal of Proteome Research

JF - Journal of Proteome Research

IS - 4

ER -

Glycosphingolipid-Glycan Signatures of Acute Myeloid Leukemia Cell Lines Reflect Hematopoietic Differentiation

Abstract

Keywords

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