ArticleEMBO molecular medicine2014
HIF factors cooperate with PML-RARα to promote acute promyelocytic leukemia progression and relapse.
Article in EMBO molecular medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- Nuclear PML expression as a prognostic biomarker in localised clear cell renal cell carcinoma.BJUI compass · 2026Article
- PML::RARα+ myeloid cells display metabolic alterations that can be targeted to treat resistant/relapse acute promyelocytic leukemias.Leukemia · 2025Article
- Targeting hypoxia-inducible factor 1α in chronic graft-versus-host disease to enhance graft-versus-leukemia responses: implications for nanotherapeutics.Frontiers in immunology · 2025Review
- Regulation of Hypoxia Dependent Reprogramming of Cancer Metabolism: Role of HIF-1 and Its Potential Therapeutic Implications in Leukemia.Asian Pacific journal of cancer prevention : APJCP · 2024Review
- A machine learning model identifies M3-like subtype in AML based on PML/RARα targets.iScience · 2024Article
- Cellular hierarchy insights reveal leukemic stem-like cells and early death risk in acute promyelocytic leukemia.Nature communications · 2024Article
- HIF-1α signaling: Essential roles in tumorigenesis and implications in targeted therapies.Genes & diseases · 2024Review
- The transcription factor HIF2α partakes in the differentiation block of acute myeloid leukemia.EMBO molecular medicine · 2023Article
- Hypoxic stress and hypoxia-inducible factors in leukemias.Frontiers in oncology · 2022Review
- The Role of Hypoxic Bone Marrow Microenvironment in Acute Myeloid Leukemia and Future Therapeutic Opportunities.International journal of molecular sciences · 2021Review
- Far from Health: The Bone Marrow Microenvironment in AML, A Leukemia Supportive Shelter.Children (Basel, Switzerland) · 2021Review
- A PML/RARα direct target atlas redefines transcriptional deregulation in acute promyelocytic leukemia.Blood · 2021Article
- The transcriptional factors HIF-1 and HIF-2 and their novel inhibitors in cancer therapy.Expert opinion on drug discovery · 2019Review
- Hypoxia-Inducible Factor1-Α (HIF1α) and Vascular Endothelial Growth Factor-A (VEGF-A) Expression in De Novo AML PatientsAsian Pacific journal of cancer prevention : APJCP · 2019Article
- Hypoxia Signaling Pathway in Stem Cell Regulation: Good and Evil.Current stem cell reports · 2018Article
- The forkhead box C1 (FOXC1) transcription factor is downregulated in acute promyelocytic leukemia.Oncotarget · 2017Article
- Integration of hypoxic HIF-α signaling in blood cancers.Oncogene · 2017Review
- The hypoxia signalling pathway in haematological malignancies.Oncotarget · 2017Review
- Hypoxia inducible factor-1α regulates a pro-invasive phenotype in acute monocytic leukemia.Oncotarget · 2016Article
- HIF-1α regulates the interaction of chronic lymphocytic leukemia cells with the tumor microenvironment.Blood · 2016Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute promyelocytic leukemia (APL) is epitomized by the chromosomal translocation t(15;17) and the resulting oncogenic fusion protein PML-RARα. Although acting primarily as a transcriptional repressor, PML-RARα can also exert functions of transcriptional co-activation. Here, we find that PML-RARα stimulates transcription driven by HIF factors, which are critical regulators of adaptive responses to hypoxia and stem cell maintenance. Consistently, HIF-related gene signatures are upregulated in leukemic promyelocytes from APL patients compared to normal promyelocytes. Through in vitro and in vivo studies, we find that PML-RARα exploits a number of HIF-1α-regulated pro-leukemogenic functions that include cell migration, bone marrow (BM) neo-angiogenesis and self-renewal of APL blasts. Furthermore, HIF-1α levels increase upon treatment of APL cells with all-trans retinoic acid (ATRA). As a consequence, inhibiting HIF-1α in APL mouse models delays leukemia progression and exquisitely synergizes with ATRA to eliminate leukemia-initiating cells (LICs).
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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.