Bioenergetic profiling of the differentiating human MDS myeloid lineage with low and high bone marrow blast counts
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- dc.contributor.author Poulaki, Aikaterini
- dc.contributor.author Katsila, Theodora
- dc.contributor.author Stergiou, Ioanna E.
- dc.contributor.author Giannouli, Stavroula
- dc.contributor.author Gόmez-Tamayo, José C.
- dc.contributor.author Piperaki, Evangelia-Theophano
- dc.contributor.author Kambas, Konstantinos
- dc.contributor.author Dimitrakopoulou, Aglaia
- dc.contributor.author Patrinos, George P.
- dc.contributor.author Tzioufas, Athanasios G.
- dc.contributor.author Voulgarelis, Michael
- dc.date.accessioned 2021-06-07T07:30:49Z
- dc.date.available 2021-06-07T07:30:49Z
- dc.date.issued 2020
- dc.description.abstract Myelodysplastic syndromes (MDS) encompass a very heterogeneous group of clonal hematopoietic stem cell differentiation disorders with malignant potential and an elusive pathobiology. Given the central role of metabolism in effective differentiation, we performed an untargeted metabolomic analysis of differentiating myeloid lineage cells from MDS bone marrow aspirates that exhibited <5% (G1) or ≥5% (G2) blasts, in order to delineate its role in MDS severity and malignant potential. Bone marrow aspirates were collected from 14 previously untreated MDS patients (G1, n = 10 and G2, n = 4) and age matched controls (n = 5). Following myeloid lineage cell isolation, untargeted mass spectrometry-based metabolomics analysis was performed. Data were processed and analyzed using Metabokit. Enrichment analysis was performed using Metaboanalyst v4 employing pathway-associated metabolite sets. We established a bioenergetic profile coordinated by the Warburg phenomenon in both groups, but with a massively different outcome that mainly depended upon its group mitochondrial function and redox state. G1 cells are overwhelmed by glycolytic intermediate accumulation due to failing mitochondria, while the functional electron transport chain and improved redox in G2 compensate for Warburg disruption. Both metabolomes reveal the production and abundance of epigenetic modifiers. G1 and G2 metabolomes differ and eventually determine the MDS clinical phenotype, as well as the potential for malignant transformation.
- dc.description.sponsorship This study was supported in part by research funding from the Special Account for Research Grants of National and Kapodistrian University of Athens, and the Hellenic Society of Hematology to M.V. This study was also partially supported by a European Commission grant (H2020-668353) awarded to G.P.P.
- dc.format.mimetype application/pdf
- dc.identifier.citation Poulaki A, Katsila T, Stergiou IE, Giannouli S, Gόmez-Tamayo JC, Piperaki ET, et al. Bioenergetic profiling of the differentiating human MDS myeloid lineage with low and high bone marrow blast counts. Cancers (Basel). 2020 Nov 26; 12(12): 3520. DOI: 10.3390/cancers12123520
- dc.identifier.doi http://dx.doi.org/10.3390/cancers12123520
- dc.identifier.issn 2072-6694
- dc.identifier.uri http://hdl.handle.net/10230/47778
- dc.language.iso eng
- dc.publisher MDPI
- dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/668353
- dc.rights Copyright © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.keyword Warburg effect
- dc.subject.keyword Acute myeloid leukemia
- dc.subject.keyword Epigenetics
- dc.subject.keyword Metabolomics
- dc.subject.keyword Mitochondria
- dc.subject.keyword Mitochondrial uncoupling
- dc.subject.keyword Myelodysplastic syndrome
- dc.subject.keyword Redox
- dc.subject.keyword Redox ratios
- dc.title Bioenergetic profiling of the differentiating human MDS myeloid lineage with low and high bone marrow blast counts
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion