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A distinct glucose metabolism signature of acute myeloid leukemia with prognostic value.
- Source :
-
Blood [Blood] 2014 Sep 04; Vol. 124 (10), pp. 1645-54. Date of Electronic Publication: 2014 Jul 08. - Publication Year :
- 2014
-
Abstract
- 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 that 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 tricarboxylic [corrected] acid cycle at gene expression level in low PRS group. In vitro results demonstrated enhanced glycolysis contributed to decreased sensitivity to antileukemic agent arabinofuranosyl cytidine (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.<br /> (© 2014 by The American Society of Hematology.)
- Subjects :
- Adolescent
Adult
Aged
Aged, 80 and over
Case-Control Studies
Cell Line, Tumor
Female
HEK293 Cells
HL-60 Cells
Humans
Male
Metabolic Networks and Pathways genetics
Middle Aged
Predictive Value of Tests
Prognosis
U937 Cells
Young Adult
Glucose metabolism
Leukemia, Myeloid, Acute diagnosis
Leukemia, Myeloid, Acute genetics
Leukemia, Myeloid, Acute metabolism
Transcriptome
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 124
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 25006128
- Full Text :
- https://doi.org/10.1182/blood-2014-02-554204