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RIPK3 Restricts Myeloid Leukemogenesis by Promoting Cell Death and Differentiation of Leukemia Initiating Cells.
Höckendorf, Ulrike; Yabal, Monica; Herold, Tobias; Munkhbaatar, Enkhtsetseg; Rott, Stephanie; Jilg, Stefanie; Kauschinger, Johanna; Magnani, Giovanni; Reisinger, Florian; Heuser, Michael; Kreipe, Hans; Sotlar, Karl; Engleitner, Thomas; Rad, Roland; Weichert, Wilko; Peschel, Christian; Ruland, Jürgen; Heikenwalder, Mathias; Spiekermann, Karsten; Slotta-Huspenina, Julia; Groß, Olaf; Jost, Philipp J.
  • Höckendorf U; III. Medical Department for Hematology and Oncology, Klinikum rechts der Isar, Technische Universität München, 81675 München, Germany.
  • Yabal M; III. Medical Department for Hematology and Oncology, Klinikum rechts der Isar, Technische Universität München, 81675 München, Germany.
  • Herold T; Department of Internal Medicine 3, University Hospital Grosshadern, Ludwig-Maximilians-Universität (LMU), 81377 München, Germany.
  • Munkhbaatar E; III. Medical Department for Hematology and Oncology, Klinikum rechts der Isar, Technische Universität München, 81675 München, Germany.
  • Rott S; III. Medical Department for Hematology and Oncology, Klinikum rechts der Isar, Technische Universität München, 81675 München, Germany.
  • Jilg S; III. Medical Department for Hematology and Oncology, Klinikum rechts der Isar, Technische Universität München, 81675 München, Germany.
  • Kauschinger J; III. Medical Department for Hematology and Oncology, Klinikum rechts der Isar, Technische Universität München, 81675 München, Germany.
  • Magnani G; Institute of Clinical Chemistry and Pathobiochemistry, Klinikum rechts der Isar, Technische Universität München, 81675 München, Germany.
  • Reisinger F; Institute of Virology, Helmholtz Zentrum München für Gesundheit und Umwelt (HMGU), 85764 Neuherberg, Germany.
  • Heuser M; Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, 30625 Hannover, Germany.
  • Kreipe H; Institute of Pathology, Hannover Medical School, 30625 Hannover, Germany.
  • Sotlar K; Institute of Pathology, Ludwig-Maximilians-University (LMU), 80337 München, Germany.
  • Engleitner T; II. Medical Department for Gastroentreology, Klinikum rechts der Isar, Technische Universität München, 81675 München, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
  • Rad R; II. Medical Department for Gastroentreology, Klinikum rechts der Isar, Technische Universität München, 81675 München, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
  • Weichert W; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Institute of Pathology, Klinikum rechts der Isar, Technische Universität München, 81675 München, Germany.
  • Peschel C; III. Medical Department for Hematology and Oncology, Klinikum rechts der Isar, Technische Universität München, 81675 München, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
  • Ruland J; Institute of Clinical Chemistry and Pathobiochemistry, Klinikum rechts der Isar, Technische Universität München, 81675 München, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
  • Heikenwalder M; Institute of Virology, Helmholtz Zentrum München für Gesundheit und Umwelt (HMGU), 85764 Neuherberg, Germany; Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
  • Spiekermann K; Department of Internal Medicine 3, University Hospital Grosshadern, Ludwig-Maximilians-Universität (LMU), 81377 München, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
  • Slotta-Huspenina J; Institute of Pathology, Klinikum rechts der Isar, Technische Universität München, 81675 München, Germany.
  • Groß O; Institute of Clinical Chemistry and Pathobiochemistry, Klinikum rechts der Isar, Technische Universität München, 81675 München, Germany.
  • Jost PJ; III. Medical Department for Hematology and Oncology, Klinikum rechts der Isar, Technische Universität München, 81675 München, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. Electronic address: philipp.jost@tum.de.
Cancer Cell ; 30(1): 75-91, 2016 07 11.
Article en En | MEDLINE | ID: mdl-27411587
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-1ß 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.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Células Madre Neoplásicas / Leucemia Mieloide Aguda / Proteína Serina-Treonina Quinasas de Interacción con Receptores Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Año: 2016 Tipo del documento: Article
Texto completo
Imprimir
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Células Madre Neoplásicas / Leucemia Mieloide Aguda / Proteína Serina-Treonina Quinasas de Interacción con Receptores Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Año: 2016 Tipo del documento: Article