Abstract
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.
Highlights
Glycosphingolipids (GSLs) are amphipathic compounds consisting of a hydrophobic ceramide backbone which is covalently linked to a hydrophilic carbohydrate residue
To reduce the complexity of each GSL glycomic profile per cell line and define technical variability of the workflow used in our study, the single mass spectrometry average composition (MSAC) was calculated (Supplementary Information, Tables S-1 and S-4) from relative abundances.[27]
A striking diversity in expression of GSL glycans was found between different acute myeloid leukemia (AML) cell lines
Summary
Glycosphingolipids (GSLs) are amphipathic compounds consisting of a hydrophobic ceramide backbone which is covalently linked to a hydrophilic carbohydrate residue. Still little is known about the gene network that coordinates the expression of GSL-synthesizing enzymes.[1,6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
