HIF-1α can act as a tumor suppressor gene in murine Acute Myeloid Leukemia.
Author
Summary, in English
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 three 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 a reconsideration of the role of HIF-1α and, as a consequence, question its generic therapeutic usefulness in AML.
Department/s
- Division of Molecular Medicine and Gene Therapy
- Division of Clinical Genetics
- Department of Experimental Medical Science
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
- StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
Publishing year
2014
Language
English
Pages
3597-3607
Publication/Series
Blood
Volume
124
Issue
24
Full text
Links
Document type
Journal article
Publisher
American Society of Hematology
Topic
- Hematology
Status
Published
ISBN/ISSN/Other
- ISSN: 1528-0020