N-acetyl-D-glucosamine is an oncometabolite modulating mast cell effector functions by chromatin remodeling

We investigated the metabolic regulation of mast cell (MC) functions to control them. MCs are sentinels of the immune system with functions involved not only in host defense but also, if not properly controlled, in MC disorders such as systemic mastocytosis (SM). We identified N-acetyl-D-glucosamine (GlcNAc or NAG) as both a circulating biomarker for SM severity and an oncometabolite that promotes uncontrolled degranulation and proliferation of MCs expressing the Kit kinase domain mutant allele, D816V, that is both an oncogene and characterizes patients with SM. Given the known role of GlcNAc-related protein glycosylation in modifying factors involved in epigenetic regulation of gene expression and the effects of GlcNAc on neoplastic MCs effector functions, we asked whether the increased susceptibility of KIT D816V MCs to GlcNAc was due to chromatin state changes. Overall design: ATAC-Sequencing of two independent experiments on ROSA KIT WT and KIT D816V human mast cells line exposed or not to 20 mM NAG (or GlcNAc) for 24h.