PUBLICATION
A metabolic interplay coordinated by HLX regulates myeloid differentiation and AML through partly overlapping pathways
- Authors
- Piragyte, I., Clapes, T., Polyzou, A., Klein Geltink, R.I., Lefkopoulos, S., Yin, N., Cauchy, P., Curtis, J.D., Klaeylé, L., Langa, X., Beckmann, C.C.A., Wlodarski, M.W., Müller, P., Van Essen, D., Rambold, A., Kapp, F.G., Mione, M., Buescher, J.M., Pearce, E.L., Polyzos, A., Trompouki, E.
- ID
- ZDB-PUB-180808-9
- Date
- 2018
- Source
- Nature communications 9: 3090 (Journal)
- Registered Authors
- Clapes, Thomas, Kapp, Friedrich, Klaeylé, Lhéanna, Lefkopoulos, Stylianos, Mione, Marina, Müller, Patrick, Trompouki, Eirini
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Survival
- Hematopoiesis
- K562 Cells
- Transcription Factors/genetics
- Transcription Factors/physiology*
- Gene Expression Regulation, Leukemic
- Zebrafish
- Autophagy
- PPAR gamma/metabolism
- Gene Expression Regulation*
- Membrane Potential, Mitochondrial
- Homeodomain Proteins/genetics
- Homeodomain Proteins/physiology*
- Humans
- Phenotype
- Signal Transduction
- Reactive Oxygen Species/metabolism
- Cell Differentiation
- Stem Cells/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/physiology*
- Hematopoietic Stem Cells/metabolism*
- Leukemia, Myeloid, Acute/genetics
- Leukemia, Myeloid, Acute/metabolism*
- Cell Proliferation
- PubMed
- 30082823 Full text @ Nat. Commun.
Citation
Piragyte, I., Clapes, T., Polyzou, A., Klein Geltink, R.I., Lefkopoulos, S., Yin, N., Cauchy, P., Curtis, J.D., Klaeylé, L., Langa, X., Beckmann, C.C.A., Wlodarski, M.W., Müller, P., Van Essen, D., Rambold, A., Kapp, F.G., Mione, M., Buescher, J.M., Pearce, E.L., Polyzos, A., Trompouki, E. (2018) A metabolic interplay coordinated by HLX regulates myeloid differentiation and AML through partly overlapping pathways. Nature communications. 9:3090.
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 PPAR? gene expression in zebrafish and human HSPCs. HLX overexpression also results in AMPK activation. Pharmacological modulation of PPAR? 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping