title: Effect of hypoxia-inducible factors in normal and leukemic stem cell regulation and their potential therapeutic impact.
abstract: BACKGROUND
  Hypoxia inducible factors (HIF-1α and HIF-2α) are the main mediators of hypoxic responses that operate in both normal and pathological conditions. Recent evidence indicates that HIF-1α and HIF-2α could have overlapping, unique and even sometimes opposing activities in both normal physiology and disease. Despite an increase in our understanding of the different pathways regulated by HIF-1α and HIF-2α, the role played by each factor in HSC maintenance and leukemogenesis is still controversial.
  
  
  METHODS
  This review summarizes our current understanding of HIF-1α and HIF-2α activities and discusses the implications and challenges of using HIF inhibitors therapeutically in blood malignancies.
  
  
  CONCLUSIONS
  As HIF inhibitors are currently under clinical evaluation in different cancers, including hematological malignancies, a more thorough understanding of the unique roles performed by HIF-1α and HIF-2α in human neoplasia is warranted.
authors.affiliation: a Haematopoietic Stem Cell Laboratory , The Francis Crick Institute , London , UK.
authors.forename: Kevin
authors.initials: K
authors.lastname: Rouault-Pierre
authors.affiliation: a Haematopoietic Stem Cell Laboratory , The Francis Crick Institute , London , UK.
authors.forename: Ashley
authors.initials: A
authors.lastname: Hamilton
authors.affiliation: a Haematopoietic Stem Cell Laboratory , The Francis Crick Institute , London , UK.
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonnet
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007938:Leukemia / Q000378:metabolism* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000099162:Endothelial PAS Domain-Containing Protein 1; C497442:HIF1A protein, human
keywords: HIFs; Hypoxia; Leukemia; Stem cell