FTY720 induces non-canonical phosphatidylserine externalization and cell death in acute myeloid leukemia.

ABSTRACT: FTY720 (fingolimod) is a FDA-approved sphingosine analog that is phosphorylated in vivo to modulate sphingosine-1-phosphate receptor (S1PR) signaling for immunosuppression in patients with refractory multiple sclerosis. FTY720 also exhibits promising anticancer efficacy in several preclinical models. While FTY720-induced cytotoxicity is not due to S1PR signaling, the mechanism remains unclear and is reported to occur through various cell death pathways. Here, we performed a systematic, mechanistic study of FTY720-induced cell death in acute myeloid leukemia (AML). We found that FTY720 induced cell death in a panel of genetically diverse AML cell lines that was accompanied by rapid phosphatidylserine (PS) externalization. Importantly, FTY720-induced PS exposure was not due to any direct eff

SUBMITTER: Young MM 

PROVIDER: S-EPMC6838108 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature