Systemic Metabolomic Profiling of Acute Myeloid Leukemia Patients before and During Disease-Stabilizing Treatment Based on All-Trans Retinoic Acid, Valproic Acid, and Low-Dose Chemotherapy

Cells

卷:8

HanneKristin Fredly¹  Øystein Bruserud²  IdaSofie Grønningsæter²  BjørnTore Gjertsen²  KimberleyJoanne Hatfield³ 

[1] Department of Medicine, Bærum Hospital, 1346 Bærum, Norway;

[2] Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway;

[3] Section for Hematology, Institute of Clinical Science, University of Bergen, 5021 Bergen, Norway;

关键词: acute myeloid leukemia;    all-trans retinoic acid;    lipids;    metabolomics;    valproic acid;   

DOI  :  10.3390/cells8101229

来源: DOAJ

【 摘 要 】

Acute myeloid leukemia (AML) is an aggressive malignancy, and many elderly/unfit patients cannot receive intensive and potentially curative therapy. These patients receive low-toxicity disease-stabilizing treatment. The combination of all-trans retinoic acid (ATRA) and the histone deacetylase inhibitor valproic acid can stabilize the disease for a subset of such patients. We performed untargeted serum metabolomic profiling for 44 AML patients receiving treatment based on ATRA and valproic acid combined with low-dose cytotoxic drugs (cytarabine, hydroxyurea, 6-mercaptopurin) which identified 886 metabolites. When comparing pretreatment samples from responders and non-responders, metabolites mainly belonging to amino acid and lipid (i.e., fatty acid) pathways were altered. Furthermore, patients with rapidly progressive disease showed an extensively altered lipid metabolism. Both ATRA and valproic acid monotherapy also altered the amino acid and lipid metabolite profiles; however, these changes were only highly significant for valproic acid treatment. Twenty-three metabolites were significantly altered by seven-day valproic acid treatment (p < 0.05, q < 0.05), where the majority of altered metabolites belonged to lipid (especially fatty acid metabolism) and amino acid pathways, including several carnitines. These metabolomic effects, and especially the effects on lipid metabolism, may be important for the antileukemic and epigenetic effects of this treatment.

【 授权许可】

Unknown