ArticleBlood2016
HIF-1α regulates the interaction of chronic lymphocytic leukemia cells with the tumor microenvironment.
Article in Blood, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
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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
42 citing papers in PubMed, 57 citations in OpenAlex.
- The evolutionary landscape of chronic lymphocytic leukemia treated with ibrutinib targeted therapy.Nature communications · 2017Trial
- The pyruvate branch point controls lymphoid cancer cell dissemination.bioRxiv : the preprint server for biology · 2026Article
- Functional differences between CLL- and ALL-derived CAR T cells in a 3D tumor microenvironment highlight CXCR4 and IL-10 as potential modulatory targets.HemaSphere · 2025Article
- Long-term adaptation of lymphoma cell lines to hypoxia is mediated by diverse molecular mechanisms that are targetable with specific inhibitors.Cell death discovery · 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
- HIF-1α signaling: Essential roles in tumorigenesis and implications in targeted therapies.Genes & diseases · 2024Review
- Cancer Stem Cells and the Tumor Microenvironment in Tumor Drug Resistance.Stem cell reviews and reports · 2023Review
- Advances in hyperbaric oxygen to promote immunotherapy through modulation of the tumor microenvironment.Frontiers in oncology · 2023Review
- Platelet-derived microparticles provoke chronic lymphocytic leukemia malignancy through metabolic reprogramming.Frontiers in immunology · 2023Article
- Adenosine 2A Receptor Activation Amplifies Ibrutinib Antiplatelet Effect; Implications in Chronic Lymphocytic Leukemia.Cancers · 2022Article
- HIF-PH Encoded byPharmaceuticals (Basel, Switzerland) · 2022Article
- Action Sites and Clinical Application of HIF-1α Inhibitors.Molecules (Basel, Switzerland) · 2022Review
- Hypoxic stress and hypoxia-inducible factors in leukemias.Frontiers in oncology · 2022Review
- Multi-platform profiling characterizes molecular subgroups and resistance networks in chronic lymphocytic leukemia.Nature communications · 2021Article
- Article
- Targeting HIF-1α Regulatory Pathways as a Strategy to Hamper Tumor-Microenvironment Interactions in CLL.Cancers · 2021Article
- Targeting of the A2A adenosine receptor counteracts immunosuppression in vivo in a mouse model of chronic lymphocytic leukemia.Haematologica · 2021Article
- HELQ and EGR3 expression correlate with IGHV mutation status and prognosis in chronic lymphocytic leukemia.Journal of translational medicine · 2021Article
- The Effect of Hypoxia on the Expression of CXC Chemokines and CXC Chemokine Receptors-A Review of Literature.International journal of molecular sciences · 2021Review
- Deciphering the Therapeutic Resistance in Acute Myeloid Leukemia.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia-inducible transcription factors (HIFs) regulate a wide array of adaptive responses to hypoxia and are often activated in solid tumors and hematologic malignancies due to intratumoral hypoxia and emerging new layers of regulation. We found that in chronic lymphocytic leukemia (CLL), HIF-1α is a novel regulator of the interaction of CLL cells with protective leukemia microenvironments and, in turn, is regulated by this interaction in a positive feedback loop that promotes leukemia survival and propagation. Through unbiased microarray analysis, we found that in CLL cells, HIF-1α regulates the expression of important chemokine receptors and cell adhesion molecules that control the interaction of leukemic cells with bone marrow and spleen microenvironments. Inactivation of HIF-1α impairs chemotaxis and cell adhesion to stroma, reduces bone marrow and spleen colonization in xenograft and allograft CLL mouse models, and prolongs survival in mice. Of interest, we found that in CLL cells, HIF-1α is transcriptionally regulated after coculture with stromal cells. Furthermore, HIF-1α messenger RNA levels vary significantly within CLL patients and correlate with the expression of HIF-1α target genes, including CXCR4, thus further emphasizing the relevance of HIF-1α expression to CLL pathogenesis.
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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.