A metabolic interplay coordinated by HLX regulates myeloid differentiation and AML through partly overlapping pathways.
Nat Commun
; 9(1): 3090, 2018 08 06.
Article
en En
| MEDLINE
| ID: mdl-30082823
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
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Células Madre Hematopoyéticas
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Leucemia Mieloide Aguda
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Regulación de la Expresión Génica
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Proteínas de Homeodominio
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Proteínas de Pez Cebra
Límite:
Animals
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Humans
Idioma:
En
Año:
2018
Tipo del documento:
Article