2-Deoxyglucose normalizes key MPN features in mice. (A) Schematic overview of 2-DG treatment in primary mice. (B-C) Spleen N-glycan analyses in vehicle- or 2-DG–treated CalrΔ52/+ mice upon 18 days of treatment, showing the top 10 most abundant N-glycans (B) and the immature high-mannose N-glycans (C). Statistical analysis performed using 1-way analysis of variance (ANOVA). Mean plus standard error of the mean (SEM). *P < .05; **P < .01. (D) Peripheral blood platelet count of vehicle- or 2-DG–treated Calr+/+ and CalrΔ52/+ mice 18 days after treatment start. Statistical analysis performed using 1-way ANOVA. Mean plus SEM. ***P < .001; ****P < .0001. (E) Megakaryocyte-erythroid progenitor (MEP) frequency. N = 7 per genotype and condition. Statistical analysis performed using 1-way ANOVA. Mean plus SEM. *P < .05. (F) MPL surface expression (normalized geometric mean) on megakaryocyte progenitors of vehicle- or 2-DG–treated Calr+/+ and CalrΔ52/+ mice. N = 3. Statistical analysis performed using 1-way ANOVA. Mean plus SEM. *P < .05. (G-H) GSEA on RNA-seq data of MEPs isolated from Calr+/+ MxCre and CalrΔ52/+ MxCre mice treated with vehicle or 2-DG. (G) GSEA showing enrichment of the Hallmark apoptosis pathway in CalrΔ52/+ MxCre MEPs from mice treated with 2-DG as compared with vehicle, whereas the opposite was found for Calr+/+ MxCre mice treated with 2-DG as compared with vehicle, shown in (H). (I) Platelet (PLT) values of Jak2V617F/+ MxCre and Jak2+/+ MxCre mice treated with 2-DG for 14 days. N = 3. Statistical analysis performed using 1-way ANOVA. *P < .05. (J) MPL surface expression (normalized geometric mean) on megakaryocyte progenitors of vehicle- or 2-DG–treated Jak2V617F/+ MxCre and Jak2+/+ MxCre mice. N = 3. Mean plus SEM. Statistical analysis performed unpaired Student t test. *P < .05. CBC, complete blood cell count; FDR, false discovery rate; NES, normalized enrichment score.