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Hif-1 alpha Deletio...
Hif-1 alpha Deletion May Lead to Adverse Treatment Effect in a Mouse Model of MLL-AF9-Driven AML
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- Velasco-Hernandez, Talia (författare)
- Lund University,Lunds universitet,Utvecklingshematopoes,Forskargrupper vid Lunds universitet,Developmental Hematopoiesis,Lund University Research Groups
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- Soneji, Shamit (författare)
- Lund University,Lunds universitet,Conputational Genomics Group,Forskargrupper vid Lunds universitet,Lund University Research Groups
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- Hidalgo, Isabel (författare)
- Lund University,Lunds universitet,Utvecklingshematopoes,Forskargrupper vid Lunds universitet,Developmental Hematopoiesis,Lund University Research Groups
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- Erlandsson, Eva (författare)
- Lund University,Lunds universitet,Utvecklingshematopoes,Forskargrupper vid Lunds universitet,Developmental Hematopoiesis,Lund University Research Groups
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- Cammenga, Jörg (författare)
- Linköping University,Linköpings universitet,Avdelningen för Kirurgi, Ortopedi och Onkologi,Medicinska fakulteten,Region Östergötland, Hematologiska kliniken US,Linköping University Hospital
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- Bryder, David (författare)
- University of Gothenburg,Lund University,Lunds universitet,Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center,Lund Univ, Sweden; Gothenburg Univ, Sweden,Utvecklingshematopoes,Forskargrupper vid Lunds universitet,Developmental Hematopoiesis,Lund University Research Groups
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(creator_code:org_t)
- Elsevier BV, 2019
- 2019
- Engelska.
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Ingår i: Stem Cell Reports. - : Elsevier BV. - 2213-6711. ; 12:1, s. 112-121
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Relapse of acute myeloid leukemia (AML) remains a significant clinical challenge due to limited therapeutic options and poor prognosis. Leukemic stem cells (LSCs) are the cellular units responsible for relapse in AML, and strategies that target LSCs are thus critical. One proposed potential strategy to this end is to break the quiescent state of LSCs, thereby sensitizing LSCs to conventional cytostatics. The hypoxia-inducible factor (HIF) pathway is a main driver of cellular quiescence and a potential therapeutic target, with precedence from both solid cancers and leukemias. Here, we used a conditional knockout Hif-1 alpha mouse model together with a standard chemotherapy regimen to evaluate LSC targeting in AML. Contrary to expectation, our studies revealed that Hif-1 alpha-deleted-leukemias displayed a faster disease progression after chemotherapy. Our studies thereby challenge the general notion of cancer stem cell sensitization by inhibition of the HIF pathway, and warrant caution when applying HIF inhibition in combination with chemotherapy in AML.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- hypoxia-inducible factor-1-alpha
- acute myeloid-leukemia
- stem-cells
- hif-2-alpha
- gene
- hif1-alpha
- survival
- hif-1
- Cell Biology
- acute myeloid leukemia
- chemotherapy
- HIF-1α
- hypoxia
- mouse model
- single-cell transcriptional analysis
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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