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A metabolic interplay coordinated by HLX regulates myeloid differentiation and AML through partly overlapping pathways

A metabolic interplay coordinated by HLX regulates myeloid differentiation and AML through partly overlapping pathways

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PIRAGYTE, Indre, Thomas CLAPES, Aikaterini POLYZOU, Ramon I. KLEIN GELTINK, Stylianos LEFKOPOULOS, Na YIN, Pierre CAUCHY, Jonathan D. CURTIS, Patrick MÜLLER, Eirini TROMPOUKI, 2018. A metabolic interplay coordinated by HLX regulates myeloid differentiation and AML through partly overlapping pathways. In: Nature communications. Nature Publishing Group. 9(1), 3090. eISSN 2041-1723. Available under: doi: 10.1038/s41467-018-05311-4

@article{Piragyte2018metab-56904, title={A metabolic interplay coordinated by HLX regulates myeloid differentiation and AML through partly overlapping pathways}, year={2018}, doi={10.1038/s41467-018-05311-4}, number={1}, volume={9}, journal={Nature communications}, author={Piragyte, Indre and Clapes, Thomas and Polyzou, Aikaterini and Klein Geltink, Ramon I. and Lefkopoulos, Stylianos and Yin, Na and Cauchy, Pierre and Curtis, Jonathan D. and Müller, Patrick and Trompouki, Eirini}, note={Article Number: 3090} }

<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#" xmlns:foaf="http://xmlns.com/foaf/0.1/" xmlns:void="http://rdfs.org/ns/void#" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/56904"> <dc:contributor>Yin, Na</dc:contributor> <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/56904/1/Piragyte_2-a9aejh0n0msj4.pdf"/> <dc:language>eng</dc:language> <dcterms:issued>2018</dcterms:issued> <dc:creator>Trompouki, Eirini</dc:creator> <dcterms:title>A metabolic interplay coordinated by HLX regulates myeloid differentiation and AML through partly overlapping pathways</dcterms:title> <dc:contributor>Klein Geltink, Ramon I.</dc:contributor> <dc:contributor>Piragyte, Indre</dc:contributor> <dc:creator>Müller, Patrick</dc:creator> <dc:contributor>Müller, Patrick</dc:contributor> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2022-03-17T11:16:24Z</dcterms:available> <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/56904"/> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2022-03-17T11:16:24Z</dc:date> <dcterms:rights rdf:resource="http://creativecommons.org/licenses/by/4.0/"/> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dc:contributor>Clapes, Thomas</dc:contributor> <dc:creator>Clapes, Thomas</dc:creator> <dc:contributor>Curtis, Jonathan D.</dc:contributor> <dc:creator>Lefkopoulos, Stylianos</dc:creator> <dc:creator>Curtis, Jonathan D.</dc:creator> <dcterms:abstract xml:lang="eng">The H2.0-like homeobox transcription factor (HLX) regulates hematopoietic differentiation and is overexpressed in Acute Myeloid Leukemia (AML), but the mechanisms underlying these functions remain unclear. We demonstrate here that HLX overexpression leads to a myeloid differentiation block both in zebrafish and human hematopoietic stem and progenitor cells (HSPCs). We show that HLX overexpression leads to downregulation of genes encoding electron transport chain (ETC) components and upregulation of PPARδ gene expression in zebrafish and human HSPCs. HLX overexpression also results in AMPK activation. Pharmacological modulation of PPARδ signaling relieves the HLX-induced myeloid differentiation block and rescues HSPC loss upon HLX knockdown but it has no effect on AML cell lines. In contrast, AMPK inhibition results in reduced viability of AML cell lines, but minimally affects myeloid progenitors. This newly described role of HLX in regulating the metabolic state of hematopoietic cells may have important therapeutic implications.</dcterms:abstract> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dc:contributor>Trompouki, Eirini</dc:contributor> <dc:contributor>Polyzou, Aikaterini</dc:contributor> <dc:contributor>Lefkopoulos, Stylianos</dc:contributor> <dc:contributor>Cauchy, Pierre</dc:contributor> <dc:creator>Klein Geltink, Ramon I.</dc:creator> <dc:creator>Cauchy, Pierre</dc:creator> <dc:rights>Attribution 4.0 International</dc:rights> <dc:creator>Polyzou, Aikaterini</dc:creator> <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/56904/1/Piragyte_2-a9aejh0n0msj4.pdf"/> <dc:creator>Piragyte, Indre</dc:creator> <dc:creator>Yin, Na</dc:creator> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> </rdf:Description> </rdf:RDF>

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