A metabolic interplay coordinated by HLX regulates myeloid differentiation and AML through partly overlapping pathways.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30082823.
- Also identified by DOI 10.1038/s41467-018-05311-4 and PMC identifier 6078963.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Gene Expression Regulation
- Hematopoietic Stem Cells
- Homeodomain Proteins
- Leukemia, Myeloid, Acute
- Transcription Factors
- Zebrafish Proteins