title: The emerging role of hypoxia, HIF-1 and HIF-2 in multiple myeloma.
abstract: Hypoxia is an imbalance between oxygen supply and demand, which deprives cells or tissues of sufficient oxygen. It is well-established that hypoxia triggers adaptive responses, which contribute to short- and long-term pathologies such as inflammation, cardiovascular disease and cancer. Induced by both microenvironmental hypoxia and genetic mutations, the elevated expression of the hypoxia-inducible transcription factor-1 (HIF-1) and HIF-2 is a key feature of many human cancers and has been shown to promote cellular processes, which facilitate tumor progression. In this review, we discuss the emerging role of hypoxia and the HIFs in the pathogenesis of multiple myeloma (MM), an incurable hematological malignancy of BM PCs, which reside within the hypoxic BM microenvironment. The need for current and future therapeutic interventions to target HIF-1 and HIF-2 in myeloma will also be discussed.
authors.affiliation: Division of Haematology, Centre for Cancer Biology, SA Pathology, CSCR, University of Adelaide, Adelaide, South Australia.
authors.forename: S K
authors.initials: SK
authors.lastname: Martin
authors.forename: P
authors.initials: P
authors.lastname: Diamond
authors.forename: S
authors.initials: S
authors.lastname: Gronthos
authors.forename: D J
authors.initials: DJ
authors.lastname: Peet
authors.forename: A C W
authors.initials: AC
authors.lastname: Zannettino
mesh_terms: D000222:Adaptation, Physiological; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology*; D001854:Bone Marrow Cells / Q000502:physiology; D015687:Cell Hypoxia; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology*; D009101:Multiple Myeloma / Q000503:physiopathology* / Q000628:therapy; 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