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

Piragyte, Indre; Clapes, Thomas; Polyzou, Aikaterini; Geltink, Ramon I. Klein; Lefkopoulos, Stylianos; Yin, Na; Cauchy, Pierre; Curtis, Jonathan D.; Klaeylé, Lhéanna; Langa, Xavier; Beckmann, Cora C. A.; Wlodarski, Marcin W.; Müller, Patrick; Essen, Dominic Van; Rambold, Angelika; Kapp, Friedrich G.; Mione, Marina; Buescher, Joerg M.; Pearce, Erika L.; Polyzos, Alexander; Trompouki, Eirini

doi:10.1038/s41467-018-05311-4

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

MPS-Authors

Piragyte, Indre
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Clapes, Thomas
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Polyzou, Aikaterini
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Geltink, Ramon I. Klein
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Lefkopoulos, Stylianos
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Yin, Na
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons204283

Cauchy, Pierre
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Curtis, Jonathan D.
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Klaeylé, Lhéanna
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Rambold, Angelika
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Buescher, Joerg M.
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Pearce, Erika L.
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons241707

Trompouki, Eirini
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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https://www.nature.com/articles/s41467-018-05311-4
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Citation

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.

Cite as: https://hdl.handle.net/21.11116/0000-0002-64B9-D

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.