| Literature DB >> 27411587 |
Ulrike Höckendorf1, Monica Yabal1, Tobias Herold2, Enkhtsetseg Munkhbaatar1, Stephanie Rott1, Stefanie Jilg1, Johanna Kauschinger1, Giovanni Magnani3, Florian Reisinger4, Michael Heuser5, Hans Kreipe6, Karl Sotlar7, Thomas Engleitner8, Roland Rad8, Wilko Weichert9, Christian Peschel10, Jürgen Ruland11, Mathias Heikenwalder12, Karsten Spiekermann13, Julia Slotta-Huspenina14, Olaf Groß3, Philipp J Jost15.
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.Entities:
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Year: 2016 PMID： 27411587 DOI： 10.1016/j.ccell.2016.06.002
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743