Targeting the hypoxia-sensing pathway in clinical hematology

Forristal, Catherine E. and Levesque, Jean-Pierre (2014) Targeting the hypoxia-sensing pathway in clinical hematology. Stem Cells Translational Medicine, 3 2: 135-140. doi:10.5966/sctm.2013-0134

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Author Forristal, Catherine E.
Levesque, Jean-Pierre
Title Targeting the hypoxia-sensing pathway in clinical hematology
Journal name Stem Cells Translational Medicine   Check publisher's open access policy
ISSN 2157-6564
Publication date 2014-02-01
Year available 2013
Sub-type Article (original research)
DOI 10.5966/sctm.2013-0134
Open Access Status DOI
Volume 3
Issue 2
Start page 135
End page 140
Total pages 6
Place of publication Durham, NC, United States
Publisher AlphaMed Press
Language eng
Formatted abstract
Hypoxia-inducible factors (HIFs) are oxygen-sensitive transcription factors regulated by oxygen-dependent prolyl hydroxylase domain (PHD) enzymes and are key to cell adaptation to low oxygen. The hematopoietic stem cell (HSC) niche in the bone marrow is highly heterogeneous in terms of microvasculature and thus oxygen concentration. The importance of hypoxia and HIFs in the hematopoietic environment is becoming increasingly recognized. Many small compounds that inhibit PHDs have been developed, enabling HIFs to be pharmacologically stabilized in an oxygen-independent manner. The use of PHD inhibitors for therapeutic intervention in hematopoiesis is being increasingly investigated. PHD inhibitors are well established to increase erythropoietin production to correct anemia in hemodialysis patients. Pharmacological stabilization of HIF-1α protein with PHD inhibitors is alsoemerging as an important regulator of HSC proliferation and self-renewal. Administration of PHD inhibitors increases quiescence and decreases proliferation of HSCs in the bone marrow in vivo, thereby protecting them fromhigh doses of irradiation and accelerating hematological recovery. Recent findings also show that stabilization of HIF-1α increases mobilization of HSCs in response to granulocyte colony-stimulating factor and plerixafor, suggesting that PHD inhibitors could be useful agents to increase mobilization success in patients requiring transplantation. These findings highlight the importance of the hypoxia-sensing pathway and HIFs in clinical hematology.
Keyword Cell & Tissue Engineering
Cell Biology
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 604303
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Research Institute-UQ (MRI-UQ)
Official 2015 Collection
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Citation counts: TR Web of Science Citation Count  Cited 10 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 11 times in Scopus Article | Citations
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