| Title : DPP8\/DPP9 inhibitor-induced pyroptosis for treatment of acute myeloid leukemia - Johnson_2018_Nat.Med_24_1151 |
| Author(s) : Johnson DC , Taabazuing CY , Okondo MC , Chui AJ , Rao SD , Brown FC , Reed C , Peguero E , de Stanchina E , Kentsis A , Bachovchin DA |
| Ref : Nat Med , 24 :1151 , 2018 |
| Abstract : Small-molecule inhibitors of the serine dipeptidases DPP8 and DPP9 (DPP8/9) induce a lytic form of cell death called pyroptosis in mouse and human monocytes and macrophages(1,2). In mouse myeloid cells, Dpp8/9 inhibition activates the inflammasome sensor Nlrp1b, which in turn activates pro-caspase-1 to mediate cell death(3), but the mechanism of DPP8/9 inhibitor-induced pyroptosis in human myeloid cells is not yet known. Here we show that the CARD-containing protein CARD8 mediates DPP8/9 inhibitor-induced pro-caspase-1-dependent pyroptosis in human myeloid cells. We further show that DPP8/9 inhibitors induce pyroptosis in the majority of human acute myeloid leukemia (AML) cell lines and primary AML samples, but not in cells from many other lineages, and that these inhibitors inhibit human AML progression in mouse models. Overall, this work identifies an activator of CARD8 in human cells and indicates that its activation by small-molecule DPP8/9 inhibitors represents a new potential therapeutic strategy for AML. |
| ESTHER : Johnson_2018_Nat.Med_24_1151 |
| PubMedSearch : Johnson_2018_Nat.Med_24_1151 |
| PubMedID: 29967349 |
| Gene_locus related to this paper: human-DPP8 , human-DPP9 |
| Gene_locus related to this paper: human-DPP8 , human-DPP9 |
Johnson DC, Taabazuing CY, Okondo MC, Chui AJ, Rao SD, Brown FC, Reed C, Peguero E, de Stanchina E, Kentsis A, Bachovchin DA (2018)
DPP8\/DPP9 inhibitor-induced pyroptosis for treatment of acute myeloid leukemia
Nat Med
24 :1151
Johnson DC, Taabazuing CY, Okondo MC, Chui AJ, Rao SD, Brown FC, Reed C, Peguero E, de Stanchina E, Kentsis A, Bachovchin DA (2018)
Nat Med
24 :1151