Editorial: Glycobiology in hematology: a promising avenue for cancer diagnostics and therapeutics

Glycobiology in hematology: a promising avenue for cancer diagnostics and therapeuticsThe 'sugar decoration' of proteins and lipids, also known as glycosylation, adds an additional dimension to their functioning and signaling in both health and disease (1).It is estimated that 50%-70% of mammalian proteins are glycosylated, which impacts on protein stability and subcellular localization.Furthermore, glycans attached to proteins or lipids expressed at the plasma membrane regulate processes like cell adhesion and immune responses.In cancer, glycosylation is commonly altered, providing potential novel therapeutic targets or diagnostic biomarkers.Such changes in glycosylation have also been described in hematological malignancies.Sanmartin-Martinez et al. reviewed the role of N-glycans in myeloid malignancies.For instance, N-glycan expression patterns differ between acute myeloid leukemia (AML) cell lines depending on their French-American-British (FAB) classification, including increased paucimannoses and alpha-L fucoses.Aberrant glycosylation profiles promote oncogenic signaling, chemoresistance, and niche hijacking.Prominent examples hereof are the glycosylation-dependent subcellular localization of fms-like tyrosine kinase 3 (FLT3) and tyrosine-protein kinase KIT in AML, and glycosylation-dependent overstimulation of MPL signaling in calreticulin mutated myeloproliferative neoplasms.Moreover, increased mannosylation and sialylation have been associated with chemoresistance in AML, by respectively stabilizing drug efflux pumps or promoting glycan-dependent binding to Eselectin, leading to niche hijacking.These findings may have clinical implications, whereby (aberrant) glycans on myeloid malignancies are promising targets for novel therapeutics, or can be used as biomarkers.Indeed, the research by Zhang et al. describes that high expression levels of genes that regulate mannosylation are associated with worse survival in patients with AML.In line with these data, mass spectrometry-based glycomics demonstrated that cytarabine (AraC)resistant AML cells express elevated levels of high mannose N-glycans, which can be Frontiers in Hematology frontiersin.