HIF-1α can act as a tumor suppressor gene in murine acute myeloid leukemia.
Blood
; 124(24): 3597-607, 2014 Dec 04.
Article
em En
| MEDLINE
| ID: mdl-25267197
ABSTRACT
Self-renewal of hematopoietic stem cells (HSCs) and leukemia-initiating cells (LICs) has been proposed to be influenced by low oxygen tension (hypoxia). This signaling, related to the cellular localization inside the bone marrow niche and/or influenced by extrinsic factors, promotes the stabilization of hypoxia-inducible factors (HIFs). Whether HIF-1α can be used as a therapeutic target in the treatment of myeloid malignancies remains unknown. We have used 3 different murine models to investigate the role of HIF-1α in acute myeloid leukemia (AML) initiation/progression and self-renewal of LICs. Unexpectedly, we failed to observe a delay or prevention of disease development from hematopoietic cells lacking Hif-1α. In contrast, deletion of Hif-1α resulted in faster development of the disease and an enhanced leukemia phenotype in some of the investigated models. Our results therefore warrant reconsideration of the role of HIF-1α and, as a consequence, question its generic therapeutic usefulness in AML.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Células-Tronco Hematopoéticas
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Leucemia Mieloide Aguda
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Genes Supressores de Tumor
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Proteínas Supressoras de Tumor
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Subunidade alfa do Fator 1 Induzível por Hipóxia
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Neoplasias Experimentais
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Blood
Ano de publicação:
2014
Tipo de documento:
Article