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Hif-1 alpha Deletion May Lead to Adverse Treatment Effect in a Mouse Model of MLL-AF9-Driven AML
Lund Univ, Sweden.
Lund Univ, Sweden.
Lund Univ, Sweden.
Lund Univ, Sweden.
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2019 (English)In: Stem Cell Reports, ISSN 2213-6711, Vol. 12, no 1, p. 112-121Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
CELL PRESS , 2019. Vol. 12, no 1, p. 112-121
National Category
Hematology
Identifiers
URN: urn:nbn:se:liu:diva-154102DOI: 10.1016/j.stemcr.2018.11.023ISI: 000455264500011PubMedID: 30595549OAI: oai:DiVA.org:liu-154102DiVA, id: diva2:1283651
Note

Funding Agencies|Sigurd och Elsa Goljes Minne Memorial Foundation; Swedish Cancer Society (Cancerfonden); Barncancerfonden; Swedish Cancer Society; Swedish Medical Research Council; ERC [Leukemiabarrier 615068]; Knut and Alice Wallenberg Foundation; Tobias Foundation

Available from: 2019-01-29 Created: 2019-01-29 Last updated: 2019-01-29

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Cammenga, Jörg
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Division of Surgery, Orthopedics and OncologyFaculty of Medicine and Health SciencesDepartment of Haematology
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CiteExportLink to record
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Citation style
  • apa
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  • de-DE
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