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

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Datum

2018

Autor:innen

Piragyte, Indre
Clapes, Thomas
Polyzou, Aikaterini
Klein Geltink, Ramon I.
Lefkopoulos, Stylianos
Yin, Na
Cauchy, Pierre
Curtis, Jonathan D.
Trompouki, Eirini
et al.

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URI (zitierfähiger Link)
http://nbn-resolving.de/urn:nbn:de:bsz:352-2-a9aejh0n0msj4
DOI (zitierfähiger Link)
https://doi.org/10.1038/s41467-018-05311-4
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CC BY 4.0

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Open Access-Veröffentlichung
Open Access Gold

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Biologie: Publikationen
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Published

Erschienen in

Nature communications. Nature Publishing Group. 2018, 9(1), 3090. eISSN 2041-1723. Available under: doi: 10.1038/s41467-018-05311-4

Zusammenfassung

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.

Zusammenfassung in einer weiteren Sprache

Fachgebiet (DDC)
570 Biowissenschaften, Biologie

Schlagwörter

Differentiation, Haematopoietic stem cells, Myelopoiesis, Transcription, Transcriptional regulatory elements

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ISO 690PIRAGYTE, 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. 2018, 9(1), 3090. eISSN 2041-1723. Available under: doi: 10.1038/s41467-018-05311-4
BibTex
@article{Piragyte2018metab-56904,
  year={2018},
  doi={10.1038/s41467-018-05311-4},
  title={A metabolic interplay coordinated by HLX regulates myeloid differentiation and AML through partly overlapping pathways},
  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}
}
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