High mobility group box 1 (HMGB1) acts as an "alarmin" to promote acute myeloid leukaemia progression
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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.
in: ONCOIMMUNOLOGY, Jahrgang 7, Nr. 6, 2018, S. e1438109.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - High mobility group box 1 (HMGB1) acts as an "alarmin" to promote acute myeloid leukaemia progression
AU - Yasinska, Inna M
AU - Gonçalves Silva, Isabel
AU - Sakhnevych, Svetlana S
AU - Ruegg, Laura
AU - Hussain, Rohanah
AU - Siligardi, Giuliano
AU - Fiedler, Walter
AU - Wellbrock, Jasmin
AU - Bardelli, Marco
AU - Varani, Luca
AU - Raap, Ulrike
AU - Berger, Steffen
AU - Gibbs, Bernhard F
AU - Fasler-Kan, Elizaveta
AU - Sumbayev, Vadim V
PY - 2018
Y1 - 2018
N2 - 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-1β) production by healthy leukocytes, leading to IL-1β-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.
AB - 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-1β) production by healthy leukocytes, leading to IL-1β-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.
KW - Journal Article
U2 - 10.1080/2162402X.2018.1438109
DO - 10.1080/2162402X.2018.1438109
M3 - SCORING: Journal article
C2 - 29872582
VL - 7
SP - e1438109
JO - ONCOIMMUNOLOGY
JF - ONCOIMMUNOLOGY
SN - 2162-402X
IS - 6
ER -
