ArticlePloS one2016
Extracellular Histone Released from Leukemic Cells Increases Their Adhesion to Endothelium and Protects them from Spontaneous and Chemotherapy-Induced Leukemic Cell Death.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Regulation of histones in thromboinflammation.Frontiers in immunology · 2026Review
- Luteolin induces apoptosis in Philadelphia chromosome-positive acute lymphoblastic leukemia cell by regulating the PI3K/AKT signaling pathway.Frontiers in pharmacology · 2025Article
- NETs - as predictors and targets of supportive therapy for cancer treatment.Frontiers in immunology · 2025Review
- A neutrophil extracellular trap-related risk score predicts prognosis and characterizes the tumor microenvironment in multiple myeloma.Scientific reports · 2024Article
- Extracellular histones trigger oxidative stress-dependent induction of the NF-kB/CAM pathway via TLR4 in endothelial cells.Journal of physiology and biochemistry · 2023Article
- Circulating Histones to Detect and Monitor the Progression of Cancer.International journal of molecular sciences · 2023Review
- Diagnostic and prognostic role of circulating neutrophil extracellular trap markers and prekallikrein in patients with high-grade serous ovarian cancer.Frontiers in oncology · 2022Article
- Characterization of the B-Cell Epitopes ofFrontiers in cellular and infection microbiology · 2022Article
- Neutrophil extracellular traps: New players in cancer research.Frontiers in immunology · 2022Review
- Histones: The critical players in innate immunity.Frontiers in immunology · 2022Review
- A narrative review of central nervous system involvement in acute leukemias.Annals of translational medicine · 2021Review
- Endogenous PAD4 in Breast Cancer Cells Mediates Cancer Extracellular Chromatin Network Formation and Promotes Lung Metastasis.Molecular cancer research : MCR · 2020Article
- Cancer cell-induced neutrophil extracellular traps promote both hypercoagulability and cancer progression.PloS one · 2019Article
- Biology, role and therapeutic potential of circulating histones in acute inflammatory disorders.Journal of cellular and molecular medicine · 2018Review
- Damage-associated molecular patterns in intensive care unit patients with acute liver injuries: A prospective cohort study.Medicine · 2018Article
- Elevated extracellular trap formation and contact system activation in acute leukemia.Journal of thrombosis and thrombolysis · 2018Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionWhen leukocytes are stimulated by reactive oxygen species (ROS), they release nuclear contents into the extracellular milieu, called by extracellular traps (ET). The nuclear contents are mainly composed of the histone-DNA complex and neutrophil elastase. This study investigated whether leukemic cells could release ET and the released histone could induce endothelial activation, eventually resulting in leukemic progression.
methodsThe circulating ET were measured in 80 patients with hematologic diseases and 40 healthy controls. ET formation and ROS levels were investigated during leukemic cell proliferation in vitro. Histone-induced endothelial adhesion molecules expression and cell survival were measured by flow cytometry.
resultsAcute leukemia patients had high levels of ET, which correlated with peripheral blast count. Leukemic cells produced high ROS levels and released extracellular histone, which was significantly blocked by antioxidants. Histone significantly induced 3 endothelial adhesion molecules expression, and promoted leukemic cell adhesion to endothelial cells, which was inhibited by histone inhibitors (heparin, polysialic acid, and activated protein C), neutralizing antibodies against these adhesion molecules, and a Toll like receptor(TLR)9 antagonist. When leukemic cells were co-cultured with endothelial cells, adherent leukemic cells showed better survival than the non-adherent ones, demonstrating that histone-treated endothelial cells protected leukemic cells from both spontaneous and chemotherapy-induced death.
conclusionOur data demonstrate for the first time that extracellular histone can be released from leukemic cells through a ROS-dependent mechanism. The released histone promotes leukemic cell adhesion by inducting the surface expression of endothelial adhesion molecules and eventually protects leukemic cells from cell death.
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