RIPK3 Restricts Myeloid Leukemogenesis by Promoting Cell Death and Differentiation of Leukemia Initiating Cells
Autor: | Jürgen Ruland, Thomas Engleitner, Enkhtsetseg Munkhbaatar, Stephanie Rott, Johanna Kauschinger, Michael Heuser, Giovanni Magnani, Philipp J. Jost, Mathias Heikenwalder, Karl Sotlar, Ulrike Höckendorf, Julia Slotta-Huspenina, Hans Kreipe, Monica Yabal, Tobias Herold, Olaf Groß, Karsten Spiekermann, Christian Peschel, Wilko Weichert, Roland Rad, Stefanie Jilg, Florian Reisinger |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Cancer Research Programmed cell death Myeloid Inflammasomes Cellular differentiation Down-Regulation Apoptosis Biology Receptors Tumor Necrosis Factor Mice 03 medical and health sciences hemic and lymphatic diseases Tumor Cells Cultured medicine Animals Humans Gene Expression Regulation Leukemic Gene Expression Profiling Myeloid leukemia Cell Differentiation Inflammasome PYCARD Neoplasms Experimental Cell Biology medicine.disease Leukemia Myeloid Acute Haematopoiesis Leukemia 030104 developmental biology medicine.anatomical_structure Oncology Receptor-Interacting Protein Serine-Threonine Kinases Immunology Neoplastic Stem Cells Cancer research medicine.drug |
Zdroj: | Cancer Cell 30, 75-91 (2016) |
ISSN: | 1535-6108 |
Popis: | 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. |
Databáze: | OpenAIRE |
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