ArticleThe Journal of experimental medicine2015
Hif-1α and Hif-2α synergize to suppress AML development but are dispensable for disease maintenance.
Article in The Journal of experimental medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Genome-wide association study identifies susceptibility loci for acute myeloid leukemia.Nature communications · 2021Pooled it
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- Leukemia-expanded splenic CD81+ erythroblasts potentiate disease progression in mice by reshaping leukemic cell metabolism.The Journal of clinical investigation · 2025Article
- The selective prolyl hydroxylase inhibitor IOX5 stabilizes HIF-1α and compromises development and progression of acute myeloid leukemia.Nature cancer · 2024Article
- From hypoxia single-cell gene signatures to HIF targeting of AML leukemic stem cells.HemaSphere · 2024Article
- Article
- The transcription factor HIF2α partakes in the differentiation block of acute myeloid leukemia.EMBO molecular medicine · 2023Article
- The Intriguing Role of Hypoxia-Inducible Factor in Myocardial Ischemia and Reperfusion: A Comprehensive Review.Journal of cardiovascular development and disease · 2023Review
- Bone Marrow Microenvironment as a Source of New Drug Targets for the Treatment of Acute Myeloid Leukaemia.International journal of molecular sciences · 2022Review
- Effects of glyphosate exposure on the miRNA expression profile and construction of the miRNA-mRNA regulatory network in mouse bone marrow cells.Functional & integrative genomics · 2022Article
- The genesis and evolution of acute myeloid leukemia stem cells in the microenvironment: From biology to therapeutic targeting.Cell death discovery · 2022Review
- Intrinsic function of the peptidylarginine deiminase PADI4 is dispensable for normal haematopoiesis.Biology open · 2022Article
- Transcriptional Regulation of Yin-Yang 1 Expression through the Hypoxia Inducible Factor-1 in Pediatric Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2022Article
- Hypoxic stress and hypoxia-inducible factors in leukemias.Frontiers in oncology · 2022Review
- Pharmacological inhibition of Carbonic Anhydrase IX and XII to enhance targeting of acute myeloid leukaemia cells under hypoxic conditions.Journal of cellular and molecular medicine · 2021Article
- Leukemia stem cell-bone marrow microenvironment interplay in acute myeloid leukemia development.Experimental hematology & oncology · 2021Review
- The Role of Hypoxic Bone Marrow Microenvironment in Acute Myeloid Leukemia and Future Therapeutic Opportunities.International journal of molecular sciences · 2021Review
- Cycling hypoxia selects for constitutive HIF stabilization.Scientific reports · 2021Article
- JMJD6 promotes self-renewal and regenerative capacity of hematopoietic stem cells.Blood advances · 2021Article
- Review
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Authors and funding
22 authors at 8 institutions in 3 countries.
Funding
Abstract
Leukemogenesis occurs under hypoxic conditions within the bone marrow (BM). Knockdown of key mediators of cellular responses to hypoxia with shRNA, namely hypoxia-inducible factor-1α (HIF-1α) or HIF-2α, in human acute myeloid leukemia (AML) samples results in their apoptosis and inability to engraft, implicating HIF-1α or HIF-2α as therapeutic targets. However, genetic deletion of Hif-1α has no effect on mouse AML maintenance and may accelerate disease development. Here, we report the impact of conditional genetic deletion of Hif-2α or both Hif-1α and Hif-2α at different stages of leukemogenesis in mice. Deletion of Hif-2α accelerates development of leukemic stem cells (LSCs) and shortens AML latency initiated by Mll-AF9 and its downstream effectors Meis1 and Hoxa9. Notably, the accelerated initiation of AML caused by Hif-2α deletion is further potentiated by Hif-1α codeletion. However, established LSCs lacking Hif-2α or both Hif-1α and Hif-2α propagate AML with the same latency as wild-type LSCs. Furthermore, pharmacological inhibition of the HIF pathway or HIF-2α knockout using the lentiviral CRISPR-Cas9 system in human established leukemic cells with MLL-AF9 translocation have no impact on their functions. We therefore conclude that although Hif-1α and Hif-2α synergize to suppress the development of AML, they are not required for LSC maintenance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.