Nature Communications (Apr 2020)
Oncogenic KrasG12D causes myeloproliferation via NLRP3 inflammasome activation
- Shaima’a Hamarsheh,
- Lena Osswald,
- Benedikt S. Saller,
- Susanne Unger,
- Donatella De Feo,
- Janaki Manoja Vinnakota,
- Martina Konantz,
- Franziska M. Uhl,
- Heiko Becker,
- Michael Lübbert,
- Khalid Shoumariyeh,
- Christoph Schürch,
- Geoffroy Andrieux,
- Nils Venhoff,
- Annette Schmitt-Graeff,
- Sandra Duquesne,
- Dietmar Pfeifer,
- Matthew A. Cooper,
- Claudia Lengerke,
- Melanie Boerries,
- Justus Duyster,
- Charlotte M. Niemeyer,
- Miriam Erlacher,
- Bruce R. Blazar,
- Burkard Becher,
- Olaf Groß,
- Tilman Brummer,
- Robert Zeiser
Affiliations
- Shaima’a Hamarsheh
- Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg
- Lena Osswald
- Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg
- Benedikt S. Saller
- Faculty of Biology, University of Freiburg
- Susanne Unger
- Institute of Experimental Immunology, University of Zurich
- Donatella De Feo
- Institute of Experimental Immunology, University of Zurich
- Janaki Manoja Vinnakota
- Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg
- Martina Konantz
- Department of Biomedicine, University of Basel and University Hospital Basel
- Franziska M. Uhl
- Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg
- Heiko Becker
- Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg
- Michael Lübbert
- Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg
- Khalid Shoumariyeh
- Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg
- Christoph Schürch
- Department of Biomedicine, University of Basel and University Hospital Basel
- Geoffroy Andrieux
- Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg
- Nils Venhoff
- Clinic for Rheumatology and Clinical Immunology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg
- Annette Schmitt-Graeff
- University of Freiburg
- Sandra Duquesne
- Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg
- Dietmar Pfeifer
- Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg
- Matthew A. Cooper
- Institute for Molecular Bioscience, University of Queensland
- Claudia Lengerke
- Department of Biomedicine, University of Basel and University Hospital Basel
- Melanie Boerries
- Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg
- Justus Duyster
- Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg
- Charlotte M. Niemeyer
- German Cancer Consortium (DKTK) Partner Site Freiburg, German Cancer Research Center (DKFZ)
- Miriam Erlacher
- German Cancer Consortium (DKTK) Partner Site Freiburg, German Cancer Research Center (DKFZ)
- Bruce R. Blazar
- Division of Blood and Marrow Transplantation, Department of Pediatrics, Masonic Cancer Center, University of Minnesota
- Burkard Becher
- Institute of Experimental Immunology, University of Zurich
- Olaf Groß
- Institute of Neuropathology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg
- Tilman Brummer
- German Cancer Consortium (DKTK) Partner Site Freiburg, German Cancer Research Center (DKFZ)
- Robert Zeiser
- Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg
- DOI
- https://doi.org/10.1038/s41467-020-15497-1
- Journal volume & issue
-
Vol. 11,
no. 1
pp. 1 – 17
Abstract
Oncogenic Ras mutations are common drivers in myeloid leukemia. Here, the authors show in patient cells and in mice that oncogenic K-Ras activates NLRP3 inflammasome to drive myeloproliferation, which can be reversed by genetic or pharmacologic NLRP3 blockade.
