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Loss of HIF-1 alpha...
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Velasco-Hernandez, T.Lund University, Sweden
(författare)
Loss of HIF-1 alpha accelerates murine FLT-3(ITD)-induced myeloproliferative neoplasia
- Artikel/kapitelEngelska2015
Förlag, utgivningsår, omfång ...
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2015-06-24
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NATURE PUBLISHING GROUP,2015
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:liu-123766
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-123766URI
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https://doi.org/10.1038/leu.2015.156DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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Funding Agencies|Barncancerfonden; Cancerfonden; SSF through the Hemato-Linne and StemTherapy consortium (Sweden); Barncancerfonden (Sweden)
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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 och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Tornero, D.Skånes University Hospital, Sweden
(författare)
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Cammenga, JörgLinköpings universitet,Avdelningen för kliniska vetenskaper,Medicinska fakulteten,Region Östergötland, Hematologiska kliniken US,Lund University, Sweden; Skånes University Hospital, Sweden(Swepub:liu)jorca02
(författare)
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Lund University, SwedenSkånes University Hospital, Sweden
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Leukemia: NATURE PUBLISHING GROUP29:12, s. 2366-23740887-69241476-5551
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Leukemia
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