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

Piragyte, I., Clapes, T., Polyzou, A., Geltink, R. I. K., Lefkopoulos, S., Yin, N., et al. (2018). A metabolic interplay coordinatd by HLX regulates myeloid differentiation and AML through partly overlapping pathways. Nature Communications, 9, 3090. doi:10.1038/s41467-018-05311-4.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0002-64B9-D Version Permalink: http://hdl.handle.net/21.11116/0000-0005-C3E0-1
Genre: Journal Article

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 Creators:
Piragyte, Indre1, Author
Clapes, Thomas1, Author
Polyzou, Aikaterini1, Author
Geltink, Ramon I. Klein1, Author
Lefkopoulos, Stylianos1, Author
Yin, Na1, Author
Cauchy, Pierre1, Author              
Curtis, Jonathan D.1, Author
Klaeylé, Lhéanna1, Author
Langa, Xavier2, Author
Beckmann, Cora C. A.2, Author
Wlodarski, Marcin W.2, Author
Müller, Patrick2, Author
Essen, Dominic Van2, Author
Rambold, Angelika1, Author              
Kapp, Friedrich G.2, Author
Mione, Marina2, Author
Buescher, Joerg M.1, Author
Pearce, Erika L.1, Author              
Polyzos, Alexander 2, Author
Trompouki, Eirini1, Author               more..
Affiliations:
1Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, 79108 Freiburg, DE, ou_2243640              
2External Organizations, ou_persistent22              

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 Abstract: 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.

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Language(s): eng - English
 Dates: 2018
 Publication Status: Published in print
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 Rev. Type: Peer
 Identifiers: DOI: 10.1038/s41467-018-05311-4
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Title: Nature Communications
  Abbreviation : Nat. Commun.
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 9 Sequence Number: - Start / End Page: 3090 Identifier: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723