ArticleCell death & disease2019
FTY720 induces non-canonical phosphatidylserine externalization and cell death in acute myeloid leukemia.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- Anticancer agent FTY720 upregulates cell cycle regulator BTG2 via the SET/TAF-Iβ -PP2A-SMAD3 signaling pathway and induces G2/M arrest in leukemia.Genes & genomics · 2026Article
- A genome-wide CRISPR/Cas9 screen reveals novel positive regulators of FTY720 sensitivity in acute lymphoblastic leukemia cells.BMC research notes · 2026Article
- The Molecular Chaperone TCP1 Affects Carcinogenicity and Is a Potential Therapeutic Target for Acute Myeloid Leukemia.Pharmaceutics · 2025Article
- Article
- Therapeutic Potential of Ceramide in Cancer Treatment.Journal of cancer research and oncobiology · 2024Article
- Pharmacological Effects of FTY720 and its Derivatives.Current topics in medicinal chemistry · 2024Review
- Acid Ceramidase Inhibitor LCL-805 Antagonizes Akt Signaling and Promotes Iron-Dependent Cell Death in Acute Myeloid Leukemia.Cancers · 2023Article
- Article
- Research Progress on Pyroptosis in Hematological Malignancies.Current treatment options in oncology · 2023Review
- Article
- A Lipid Perspective on Regulated Pyroptosis.International journal of biological sciences · 2023Review
- Harnessing the power of sphingolipids: Prospects for acute myeloid leukemia.Blood reviews · 2022Review
- A novel ferroptosis-related gene signature can predict prognosis and influence immune microenvironment in acute myeloid leukemia.Bosnian journal of basic medical sciences · 2022Article
- Review
- Oncolytic Herpes Simplex Virus Type 1 Induces Immunogenic Cell Death Resulting in Maturation of BDCA-1International journal of molecular sciences · 2022Article
- Sphingolipid metabolism in T cell responses after allogeneic hematopoietic cell transplantation.Frontiers in immunology · 2022Review
- Antileukemic Natural Product Induced Both Apoptotic and Pyroptotic Programmed Cell Death and Differentiation Effect.International journal of molecular sciences · 2021Article
- Article
- Lipid composition of the cancer cell membrane.Journal of bioenergetics and biomembranes · 2020Review
- Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
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 effects on plasma membrane integrity and was independent of canonical signaling by regulated cell death pathways known to activate lipid flip-flop, including caspase-dependent apoptosis/pyroptosis, necroptosis, ferroptosis, and reactive oxygen species-mediated cell death. Notably, PS exposure required cellular vacuolization induced by defects in endocytic trafficking and was suppressed by the inhibition of PP2A and shedding of Annexin V-positive subcellular particles. Collectively, our studies reveal a non-canonical pathway underlying PS externalization and cell death in AML to provide mechanistic insight into the antitumor properties of FTY720.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.