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dc.contributor.authorGrønningsæter, Ida Sofieen_US
dc.contributor.authorFredly, Hanne Kristinen_US
dc.contributor.authorGjertsen, Bjørn Toreen_US
dc.contributor.authorHatfield, Kimberley Joanneen_US
dc.contributor.authorBruserud, Øysteinen_US
dc.date.accessioned2020-05-29T16:44:11Z
dc.date.available2020-05-29T16:44:11Z
dc.date.issued2019-10-10
dc.PublishedGrønningsæter IS, Fredly HK, Gjertsen BT, Hatfield KJ, Bruserud Ø. 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. 2019;8:1229eng
dc.identifier.issn2073-4409
dc.identifier.urihttps://hdl.handle.net/1956/22422
dc.description.abstractAcute 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.en_US
dc.language.isoengeng
dc.publisherMDPIeng
dc.rightsAttribution CC BYeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/eng
dc.subjectAcute myeloid leukemiaeng
dc.subjectall-trans retinoic acideng
dc.subjectlipidseng
dc.subjectMetabolomicseng
dc.subjectvalproic acideng
dc.titleSystemic Metabolomic Profiling of Acute Myeloid Leukemia Patients before and During Disease-Stabilizing Treatment Based on All-Trans Retinoic Acid, Valproic Acid, and Low-Dose Chemotherapyen_US
dc.typePeer reviewed
dc.typeJournal article
dc.date.updated2020-02-04T15:08:02Z
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2019 The Author(s)
dc.identifier.doihttps://doi.org/10.3390/cells8101229
dc.identifier.cristin1788749
dc.source.journalCells


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