炎症体
白血病
髓系白血病
程序性细胞死亡
癌症研究
髓样
生物
免疫学
医学
细胞凋亡
炎症
遗传学
作者
Ulrike Höckendorf,Monica Yabal,Tobias Herold,Enkhtsetseg Munkhbaatar,Stephanie Rott,Stefanie Jilg,Johanna Kauschinger,Giovanni Magnani,Florian Reisinger,Michael Heuser,Hans Kreipe,Karl Sotlar,Thomas Engleitner,Roland Rad,Wilko Weichert,Christian Peschel,Jürgen Ruland,Mathias Heikenwälder,Karsten Spiekermann,Julia Slotta‐Huspenina,Olaf Groß,Philipp J. Jost
出处
期刊:Cancer Cell
[Elsevier]
日期:2016-07-01
卷期号:30 (1): 75-91
被引量:143
标识
DOI:10.1016/j.ccell.2016.06.002
摘要
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.
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