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

Di Wang | Zendy; Tao Zhang | Zendy; Katarina Madunić | Zendy; Antonius A. de Waard | Zendy; Constantin Blöchl | Zendy; Oleg A. Mayboroda | Zendy; Marieke Griffioen | Zendy; Robbert M. Spaapen | Zendy; Christian G. Huber | Zendy; Guinevere S. M. LageveenKammeijer | Zendy; Manfred Wuhrer | Zendy

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

Author(s) -

Di Wang,

Tao Zhang,

Katarina Madunić,

Antonius A. de Waard,

Constantin Blöchl,

Oleg A. Mayboroda,

Marieke Griffioen,

Robbert M. Spaapen,

Christian G. Huber,

Guinevere S. M. LageveenKammeijer,

Manfred Wuhrer

Publication year - 2022

Publication title -

journal of proteome research

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.644

H-Index - 161

eISSN - 1535-3907

pISSN - 1535-3893

DOI - 10.1021/acs.jproteome.1c00911

Subject(s) - myeloid leukemia , glycan , glycomics , biology , gata2 , glycosphingolipid , transcriptome , glycosylation , haematopoiesis , myeloid , runx1 , transcription factor , cell culture , glycome , gene expression , microbiology and biotechnology , chemistry , biochemistry , gene , cancer research , stem cell , glycoprotein , genetics

Aberrant expression of certain glycosphingolipids (GSLs) is associated with the differentiation of acute myeloid leukemia (AML) cells. However, the expression patterns of GSLs in AML are still poorly explored because of their complexity, the presence of multiple isomeric structures, and tedious analytical procedures. In this study, we performed an in-depth GSL glycan analysis of 19 AML cell lines using porous graphitized carbon liquid chromatography-mass spectrometry revealing strikingly different GSL glycan profiles between the various AML cell lines. The cell lines of the M6 subtype showed a high expression of gangliosides with α2,3-sialylation and Neu5Gc, while the M2 and M5 subtypes were characterized by high expression of (neo)lacto-series glycans and Lewis A/X antigens. Integrated analysis of glycomics and available transcriptomics data revealed the association of GSL glycan abundances with the transcriptomics expression of certain glycosyltransferases (GTs) and transcription factors (TFs). In addition, correlations were found between specific GTs and TFs. Our data reveal TFs GATA2 , GATA1 , and RUNX1 as candidate inducers of the expression of gangliosides and sialylation via regulation of the GTs ST3GAL2 and ST8SIA1 . In conclusion, we show that GSL glycan expression levels are associated with hematopoietic AML classifications and TF and GT gene expression. Further research is needed to dissect the regulation of GSL expression and its role in hematopoiesis and associated malignancies.

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