Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Höckendorf, U; Yabal, M; Herold, T; Munkhbaatar, E; Rott, S; Jilg, S; Kauschinger, J; Magnani, G; Reisinger, F; Heuser, M; Kreipe, H; Sotlar, K; Engleitner, T; Rad, R; Weichert, W; Peschel, C; Ruland, J; Heikenwalder, M; Spiekermann, K; Slotta-Huspenina, J; Groß, O; Jost, PJ.
RIPK3 Restricts Myeloid Leukemogenesis by Promoting Cell Death and Differentiation of Leukemia Initiating Cells.
Cancer Cell. 2016; 30(1):75-91
Doi: 10.1016/j.ccell.2016.06.002
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- Führende Autor*innen der Med Uni Graz
- Jost Philipp
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- Abstract:
- Since acute myeloid leukemia (AML) is characterized by the blockade of hematopoietic differentiation and cell death, we interrogated RIPK3 signaling in AML development. Genetic loss of Ripk3 converted murine FLT3-ITD-driven myeloproliferation into an overt AML by enhancing the accumulation of leukemia-initiating cells (LIC). Failed inflammasome activation and cell death mediated by tumor necrosis factor receptor caused this accumulation of LIC exemplified by accelerated leukemia onset in Il1r1(-/-), Pycard(-/-), and Tnfr1/2(-/-) mice. RIPK3 signaling was partly mediated by mixed lineage kinase domain-like. This link between suppression of RIPK3, failed interleukin-1β release, and blocked cell death was supported by significantly reduced RIPK3 in primary AML patient cohorts. Our data identify RIPK3 and the inflammasome as key tumor suppressors in AML. Copyright © 2016 Elsevier Inc. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Apoptosis -
- Cell Differentiation -
- Down-Regulation -
- Gene Expression Profiling - methods
- Gene Expression Regulation, Leukemic -
- Humans -
- Inflammasomes - metabolism
- Leukemia, Myeloid, Acute - genetics
- Leukemia, Myeloid, Acute - metabolism
- Leukemia, Myeloid, Acute - pathology
- Mice -
- Neoplasms, Experimental -
- Neoplastic Stem Cells - cytology
- Receptor-Interacting Protein Serine-Threonine Kinases - genetics
- Receptor-Interacting Protein Serine-Threonine Kinases - metabolism
- Receptors, Tumor Necrosis Factor - metabolism
- Tumor Cells, Cultured -