Metabolomic alterations associated with systemic mastocytosis severity. (A) Principal component analysis (PCA) of metabolites measured in indolent (green) and advanced (orange) SM plasma samples. (B) Indolent SM-based z-score plot of 59 metabolites significantly deregulated between samples from patients with ISM and AdvSM. Each dot represents 1 metabolite in 1 SM sample, and the color indicates the disease form (light green: indolent; red: advanced) (C) Metabolome view from pathway analysis performed using MetaboAnalyst 4.0. Each circle represents a different pathway, and the circle size and color shade indicate the pathway impact and P value (with red being the most significant), respectively. Selected pathways with high impact and/or high P values are labeled 1 to 7. (D) Pathway covering using HumanCyc showing the smallest pathways including differential metabolites. (E) Outline of the transcriptomic approach used to highlight significant dysregulated metabolic transcripts in sorted bone marrow mast cells (MCs) from patients with SM. (F) Enrichment of overactivated pathways between different groups of patients with SM, as identified by Enrich. The adjusted P values are shown as −log (P) values on the x-axis.