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HIF-1α can act as a tumor suppressor gene in murine Acute Myeloid Leukemia.

Velasco, Talia LU ; Hyrenius Wittsten, Axel LU ; Rehn, Matilda LU ; Bryder, David LU and Cammenga, Jörg LU (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)
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author
organization
publishing date
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
ISSN
1528-0020
DOI
10.1182/blood-2014-04-567065
language
English
LU publication?
yes
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
2014-11-04 18:26:23
date last changed
2017-11-19 03:14:08
@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          = {http://dx.doi.org/10.1182/blood-2014-04-567065},
  volume       = {124},
  year         = {2014},
}