Loss of HIF-1α accelerates murine FLT-3ITD-induced myeloproliferative neoplasia.
(2015) In Leukemia 29(12). p.2366-2374- Abstract
- Hypoxia-induced signaling is important for normal and malignant hematopoiesis. The transcription factor hypoxia-inducible factor-1α (HIF-1α) plays a crucial role in quiescence and self-renewal of hematopoietic stem cells (HSCs) as well as leukemia-initiating cells (LICs) of acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). We have investigated the effect of HIF-1α loss on the phenotype and biology of FLT-3(ITD)-induced myeloproliferative neoplasm (MPN). Using transgenic mouse models, we show that deletion of HIF-1α leads to an enhanced MPN phenotype reflected by higher numbers of white blood cells, more severe splenomegaly and decreased survival. The proliferative effect of HIF-1α loss is cell-intrinsic as shown by... (More)
- Hypoxia-induced signaling is important for normal and malignant hematopoiesis. The transcription factor hypoxia-inducible factor-1α (HIF-1α) plays a crucial role in quiescence and self-renewal of hematopoietic stem cells (HSCs) as well as leukemia-initiating cells (LICs) of acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). We have investigated the effect of HIF-1α loss on the phenotype and biology of FLT-3(ITD)-induced myeloproliferative neoplasm (MPN). Using transgenic mouse models, we show that deletion of HIF-1α leads to an enhanced MPN phenotype reflected by higher numbers of white blood cells, more severe splenomegaly and decreased survival. The proliferative effect of HIF-1α loss is cell-intrinsic as shown by transplantation into recipient mice. HSCs loss and organ specific changes in number and percentage of long-term hematopoietic stem cells (LT-HSCs) were the most pronounced effects on a cellular level after HIF-1α deletion. Furthermore, we found a metabolic hyperactivation of malignant cells in the spleen upon loss of HIF-1α. Some of our findings are in contrary to what has been previously described for the role of HIF-1α in other myeloid hematologic malignancies and question the potential of HIF-1α as a therapeutic target.Leukemia accepted article preview online, 24 June 2015. doi:10.1038/leu.2015.156. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/7478120
- author
- Velasco, Talia LU ; Tornero Prieto, Daniel LU and Cammenga, Jörg LU
- organization
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Leukemia
- volume
- 29
- issue
- 12
- pages
- 2366 - 2374
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:26104662
- wos:000366393900011
- scopus:84949883363
- pmid:26104662
- ISSN
- 1476-5551
- DOI
- 10.1038/leu.2015.156
- language
- English
- LU publication?
- yes
- id
- a7ebf8c1-5228-410e-a96b-eed8d4965e35 (old id 7478120)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/26104662?dopt=Abstract
- date added to LUP
- 2016-04-01 10:23:21
- date last changed
- 2022-04-27 21:35:14
@article{a7ebf8c1-5228-410e-a96b-eed8d4965e35,
abstract = {{Hypoxia-induced signaling is important for normal and malignant hematopoiesis. The transcription factor hypoxia-inducible factor-1α (HIF-1α) plays a crucial role in quiescence and self-renewal of hematopoietic stem cells (HSCs) as well as leukemia-initiating cells (LICs) of acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). We have investigated the effect of HIF-1α loss on the phenotype and biology of FLT-3(ITD)-induced myeloproliferative neoplasm (MPN). Using transgenic mouse models, we show that deletion of HIF-1α leads to an enhanced MPN phenotype reflected by higher numbers of white blood cells, more severe splenomegaly and decreased survival. The proliferative effect of HIF-1α loss is cell-intrinsic as shown by transplantation into recipient mice. HSCs loss and organ specific changes in number and percentage of long-term hematopoietic stem cells (LT-HSCs) were the most pronounced effects on a cellular level after HIF-1α deletion. Furthermore, we found a metabolic hyperactivation of malignant cells in the spleen upon loss of HIF-1α. Some of our findings are in contrary to what has been previously described for the role of HIF-1α in other myeloid hematologic malignancies and question the potential of HIF-1α as a therapeutic target.Leukemia accepted article preview online, 24 June 2015. doi:10.1038/leu.2015.156.}},
author = {{Velasco, Talia and Tornero Prieto, Daniel and Cammenga, Jörg}},
issn = {{1476-5551}},
language = {{eng}},
number = {{12}},
pages = {{2366--2374}},
publisher = {{Nature Publishing Group}},
series = {{Leukemia}},
title = {{Loss of HIF-1α accelerates murine FLT-3ITD-induced myeloproliferative neoplasia.}},
url = {{https://lup.lub.lu.se/search/files/1803508/8838246.pdf}},
doi = {{10.1038/leu.2015.156}},
volume = {{29}},
year = {{2015}},
}