A distinct glucose metabolism signature of acute myeloid leukemia with prognostic value Running title: The glucose metabolism signature of acute myeloid leukemia

Acute myeloid leukemia (AML) is a group of hematological malignancies with high heterogeneity. There is an increasing need to improve the risk stratification of AML patients including those with normal cytogenetics, using molecular biomarkers. Here, we report a metabolomics study which identified a distinct glucose metabolism signature with 400 AML patients and 446 healthy controls. The glucose metabolism signature comprises a panel of 6 serum metabolite markers, which demonstrated prognostic value in cytogenetically normal AML patients. We generated a prognosis-risk score (PRS) with 6 metabolite markers for each patient using principal component analysis. A low PRS was able to predict patients with poor survival independently of well-established markers. We further compared the gene-expression patterns of AML blast cells between low and high PRS groups, which correlated well to the metabolic pathways involving the 6 metabolite markers, with enhanced glycolysis and TCA cycle at geneexpression level in low PRS group. In vitro results demonstrated enhanced glycolysis contributed to decreased sensitivity to anti-leukemic agent Ara-C, whereas inhibition of glycolysis suppressed AML cell proliferation and potentiated cytotoxicity of Ara-C. Our study provides strong evidence for the use of serum metabolites and metabolic pathways as novel prognostic markers and potential therapeutic targets for AML. For personal use only. on April 13, 2017. by guest www.bloodjournal.org From