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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
; ; ; and
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
  • 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}},
}