NLRP3 Inflammasome Promotes the Progression of Acute Myeloid Leukemia via IL-1β Pathway

NLRP3 inflammasome has been reported to be associated with the pathogenesis of multiple solid tumors. However, the role of NLRP3 inflammasome in acute myeloid leukemia (AML) remains unclear. We showed that NLRP3 inflammasome is over-expressed and highly activated in AML bone marrow leukemia cells, which is correlated with poor prognosis. The activation of NLRP3 inflammasome in AML cells promotes leukemia cells proliferation, inhibits apoptosis and increases resistance to chemotherapy, while inactivation of NLRP3 by caspase-1 or NF-kappa B inhibitor shows leukemia-suppressing effects. Bayesian networks analysis and cell co-culture tests further suggest that NLRP3 inflammasome acts through IL-1 beta but not IL-18 in AML. Knocking down endogenous IL-1 beta or anti-IL-1 beta antibody inhibits leukemia cells whereas IL-1 beta cytokine enhances leukemia proliferation. In AML murine model, up-regulation of NLRP3 increases the leukemia burden in bone marrow, spleen and liver, and shortens the survival time; furthermore, knocking out NLRP3 inhibits leukemia progression. Collectively, all these evidences demonstrate that NLRP3 inflammasome promotes AML progression in an IL-1 beta dependent manner, and targeting NLRP3 inflammasome may provide a novel therapeutic option for AML.

Automated summary

NLRP3 inflammasome is over-expressed and highly activated in AML bone marrow leukemia cells, promoting leukemia cell proliferation, inhibiting apoptosis and increasing resistance to chemotherapy. IL-1 beta plays a crucial role in this process. Targeting NLRP3 inflammasome may offer a novel therapeutic option for AML.