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Loss of HIF-1 alpha...
Loss of HIF-1 alpha accelerates murine FLT-3(ITD)-induced myeloproliferative neoplasia
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- Velasco-Hernandez, T. (författare)
- Lund University, Sweden
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- Tornero, D. (författare)
- Skånes University Hospital, Sweden
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- Cammenga, Jörg (författare)
- Linköpings universitet,Avdelningen för kliniska vetenskaper,Medicinska fakulteten,Region Östergötland, Hematologiska kliniken US,Lund University, Sweden; Skånes University Hospital, Sweden
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(creator_code:org_t)
- 2015-06-24
- 2015
- Engelska.
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Ingår i: Leukemia. - : NATURE PUBLISHING GROUP. - 0887-6924 .- 1476-5551. ; 29:12, s. 2366-2374
- Relaterad länk:
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https://www.nature.c...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Hypoxia-induced signaling is important for normal and malignant hematopoiesis. The transcription factor hypoxia-inducible factor-1 alpha (HIF-1 alpha) has a crucial role in quiescence and self-renewal of hematopoietic stem cells (HSCs), as well as leukemia-initiating cells (LICs) of acute myeloid leukemia and chronic myeloid leukemia. We have investigated the effect of HIF-1 alpha loss on the phenotype and biology of FLT-3(ITD)-induced myeloproliferative neoplasm (MPN). Using transgenic mouse models, we show that deletion of HIF-1 alpha leads to an enhanced MPN phenotype reflected by an increased number of white blood cells, more severe splenomegaly and decreased survival. The proliferative effect of HIF-1 alpha loss is cell intrinsic as shown by transplantation into recipient mice. HSC loss and organ-specific changes in the number and percentage of long-term HSCs were the most pronounced effects on a cellular level after HIF-1 alpha deletion. Furthermore, we found a metabolic hyperactivation of malignant cells in the spleen upon loss of HIF-1 alpha. Some of our findings are in contrary to what has been previously described for the role of HIF-1 alpha in other myeloid hematologic malignancies and question the potential of HIF-1 alpha as a therapeutic target.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Publikations- och innehållstyp
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- art (ämneskategori)
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