HIF-1α can act as a tumor suppressor gene in murine Acute Myeloid Leukemia.
(2014) In Blood 124(24). p.3597-3607- 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 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4738785
- author
- Velasco, Talia LU ; Hyrenius Wittsten, Axel LU ; Rehn, Matilda LU ; Bryder, David LU and Cammenga, Jörg LU
- organization
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Blood
- volume
- 124
- issue
- 24
- pages
- 3597 - 3607
- publisher
- American Society of Hematology
- external identifiers
-
- pmid:25267197
- wos:000347465900016
- scopus:84915733840
- pmid:25267197
- ISSN
- 1528-0020
- DOI
- 10.1182/blood-2014-04-567065
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Stem Cell Aging (013212073), Division of Clinical Genetics (013022003), Division of Molecular Medicine and Gene Therapy (013022010)
- id
- 9be3b295-15f2-41cc-ab1d-5282130ac99d (old id 4738785)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/25267197?dopt=Abstract
- date added to LUP
- 2016-04-01 10:38:59
- date last changed
- 2022-04-28 00:00:02
@article{9be3b295-15f2-41cc-ab1d-5282130ac99d, 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 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.}}, author = {{Velasco, Talia and Hyrenius Wittsten, Axel and Rehn, Matilda and Bryder, David and Cammenga, Jörg}}, issn = {{1528-0020}}, language = {{eng}}, number = {{24}}, pages = {{3597--3607}}, publisher = {{American Society of Hematology}}, series = {{Blood}}, title = {{HIF-1α can act as a tumor suppressor gene in murine Acute Myeloid Leukemia.}}, url = {{https://lup.lub.lu.se/search/files/2019357/5463065.pdf}}, doi = {{10.1182/blood-2014-04-567065}}, volume = {{124}}, year = {{2014}}, }