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High mobility group box 1 (HMGB1) acts as an "alarmin" to promote acute myeloid leukaemia progression.
Yasinska, Inna M; Gonçalves Silva, Isabel; Sakhnevych, Svetlana S; Ruegg, Laura; Hussain, Rohanah; Siligardi, Giuliano; Fiedler, Walter; Wellbrock, Jasmin; Bardelli, Marco; Varani, Luca; Raap, Ulrike; Berger, Steffen; Gibbs, Bernhard F; Fasler-Kan, Elizaveta; Sumbayev, Vadim V.
Afiliação
  • Yasinska IM; Medway School of Pharmacy, Universities of Kent and Greenwich, Chatham Maritime, United Kingdom.
  • Gonçalves Silva I; Medway School of Pharmacy, Universities of Kent and Greenwich, Chatham Maritime, United Kingdom.
  • Sakhnevych SS; Medway School of Pharmacy, Universities of Kent and Greenwich, Chatham Maritime, United Kingdom.
  • Ruegg L; Medway School of Pharmacy, Universities of Kent and Greenwich, Chatham Maritime, United Kingdom.
  • Hussain R; Beamline 23, Diamond Light Source, Didcot, UK.
  • Siligardi G; Beamline 23, Diamond Light Source, Didcot, UK.
  • Fiedler W; Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald University Cancer Center, University Medical Center Hamburg-Eppendorf, Germany.
  • Wellbrock J; Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald University Cancer Center, University Medical Center Hamburg-Eppendorf, Germany.
  • Bardelli M; Institute for Research in Biomedicine, Universita' della Svizzera italiana (USI), Bellinzona, Switzerland.
  • Varani L; Institute for Research in Biomedicine, Universita' della Svizzera italiana (USI), Bellinzona, Switzerland.
  • Raap U; Department of Medicine (Dermatology and Allergology), University of Oldenburg, Germany.
  • Berger S; Department of Pediatric Surgery and Department of Biomedical Research, Children's Hospital, Inselspital, University of Bern, Switzerland.
  • Gibbs BF; Department of Medicine (Dermatology and Allergology), University of Oldenburg, Germany.
  • Fasler-Kan E; Medway School of Pharmacy, Universities of Kent and Greenwich, Chatham Maritime, United Kingdom.
  • Sumbayev VV; Department of Pediatric Surgery and Department of Biomedical Research, Children's Hospital, Inselspital, University of Bern, Switzerland.
Oncoimmunology ; 7(6): e1438109, 2018.
Article em En | MEDLINE | ID: mdl-29872582
High mobility group box 1 (HMGB1) is a non-histone protein localised in the cell nucleus, where it interacts with DNA and promotes nuclear transcription events. HMGB1 levels are elevated during acute myeloid leukaemia (AML) progression followed by participation of this protein in triggering signalling events in target cells as a pro-inflammatory stimulus. This mechanism was hypothesised to be employed as a survival pathway by malignant blood cells and our aims were therefore to test this hypothesis experimentally. Here we report that HMGB1 triggers the release of tumour necrosis factor alpha (TNF-α) by primary human AML cells. TNF-α induces interleukin 1 beta (IL-1ß) production by healthy leukocytes, leading to IL-1ß-induced secretion of stem cell factor (SCF) by competent cells (for example endothelial cells). These results were verified in mouse bone marrow and primary human AML blood plasma samples. In addition, HMGB1 was found to induce secretion of angiogenic vascular endothelial growth factor (VEGF) and this process was dependent on the immune receptor Tim-3. We therefore conclude that HMGB1 is critical for AML progression as a ligand of Tim-3 and other immune receptors thus supporting survival/proliferation of AML cells and possibly the process of angiogenesis.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2018 Tipo de documento: Article