HIF-1α can act as a tumor suppressor gene in murine Acute Myeloid Leukemia.

Talia Velasco, Axel Hyrenius Wittsten, Matilda Rehn, David Bryder, Jörg Cammenga

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Abstract

Self-renewal of hematopoietic stem cells (HSCs) and leukemia-initiating cells (LICs) has been proposed to be influenced by low oxygen tension (hypoxia). This signaling, related to the cellular localization inside the bone marrow niche and/or influenced by extrinsic factors, promotes the stabilization of hypoxia inducible factors (HIFs). Whether HIF-1α can be used as a therapeutic target in the treatment of myeloid malignancies remains unknown. We have used three different murine models to investigate the role of HIF-1α in acute myeloid leukemia (AML) initiation/progression and self-renewal of LICs. Unexpectedly, we failed to observe a delay or prevention of disease development from hematopoietic cells lacking Hif-1α. In contrast, deletion of Hif-1α resulted in faster development of the disease and an enhanced leukemia phenotype in some of the investigated models. Our results therefore warrant a reconsideration of the role of HIF-1α and, as a consequence, question its generic therapeutic usefulness in AML.
Original languageEnglish
Pages (from-to)3597-3607
JournalBlood
Volume124
Issue number24
DOIs
Publication statusPublished - 2014

Bibliographical note

The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Stem Cell Aging (013212073), Division of Clinical Genetics (013022003), Division of Molecular Medicine and Gene Therapy (013022010)

Subject classification (UKÄ)

  • Hematology

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