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... Show moreAberrant 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. Show less
Blochl, C.; Wang, D.; Madunic, K.; Lageveen-Kammeijer, G.S.M.; Huber, C.G.; Wuhrer, M.; Zhang, T. 2021
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... Show moreAcute 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-MS2), 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. Show less
