ArticleBlood2013
Antagonistic activities of the immunomodulator and PP2A-activating drug FTY720 (Fingolimod, Gilenya) in Jak2-driven hematologic malignancies.
Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 69 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 109 citations in OpenAlex.
- A systematic evaluation of the safety and toxicity of fingolimod for its potential use in the treatment of acute myeloid leukaemia.Anti-cancer drugs · 2016Pooled it
- Targeting MYC-Driven Cancers: From Oncogenic Addiction to Therapeutic Vulnerability.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Decreased PP2A expression and activity represent a therapeutic target for plexiform neurofibroma.Acta neuropathologica communications · 2026Article
- Bicaudal‑C1 in Cancer: Molecular Mechanisms and Therapeutic Strategies Integrating Chinese and Western Medicine.Drug design, development and therapy · 2026Review
- Targeting PP2A in cancer: an underrated option.Journal of experimental & clinical cancer research : CR · 2025Review
- Merkel Cell Polyomavirus targets SET/PP2A complex to promote cellular proliferation and migration.Virology · 2024Article
- Altering phosphorylation in cancer through PP2A modifiers.Cancer cell international · 2024Review
- Oncoprotein SET dynamically regulates cellular stress response through nucleocytoplasmic transport in breast cancer.Cell biology and toxicology · 2023Article
- Targeting PP2A-dependent autophagy enhances sensitivity to ruxolitinib in JAK2Blood cancer journal · 2023Article
- The Effects of Protein Phosphatase 2A Activation with Novel Tricyclic Sulfonamides on Hepatoblastoma.Journal of pediatric surgery · 2023Article
- Article
- Thirty years of SET/TAF1β/I2PP2A: from the identification of the biological functions to its implications in cancer and Alzheimer's disease.Bioscience reports · 2022Review
- Review
- Article
- Recent Progress in the Development of Opaganib for the Treatment of Covid-19.Drug design, development and therapy · 2022Review
- Potential of phenothiazines to synergistically block calmodulin and reactivate PP2A in cancer cells.PloS one · 2022Article
- Isolation of Primary Hepatocytes for Testing Tumor Penetrating Peptides.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Multiple sclerosis is linked to MAPKJournal of molecular medicine (Berlin, Germany) · 2021Review
- Stathmin dynamics modulate the activity of eribulin in breast cancer cells.Pharmacology research & perspectives · 2021Article
- FTY720 Inhibits Expansion of Breast Cancer Stem Cells via PP2A Activation.International journal of molecular sciences · 2021Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
26 authors at 10 institutions in 3 countries.
Funding
Abstract
FTY720 (Fingolimod, Gilenya) is a sphingosine analog used as an immunosuppressant in multiple sclerosis patients. FTY720 is also a potent protein phosphatase 2A (PP2A)-activating drug (PAD). PP2A is a tumor suppressor found inactivated in different types of cancer. We show here that PP2A is inactive in polycythemia vera (PV) and other myeloproliferative neoplasms characterized by the expression of the transforming Jak2(V617F) oncogene. PP2A inactivation occurs in a Jak2(V617F) dose/kinase-dependent manner through the PI-3Kγ-PKC-induced phosphorylation of the PP2A inhibitor SET. Genetic or PAD-mediated PP2A reactivation induces Jak2(V617F) inactivation/downregulation and impairs clonogenic potential of Jak2(V617F) cell lines and PV but not normal CD34(+) progenitors. Likewise, FTY720 decreases leukemic allelic burden, reduces splenomegaly, and significantly increases survival of Jak2(V617F) leukemic mice without adverse effects. Mechanistically, we show that in Jak2(V617F) cells, FTY720 antileukemic activity requires neither FTY720 phosphorylation (FTY720-P) nor SET dimerization or ceramide induction but depends on interaction with SET K209. Moreover, we show that Jak2(V617F) also utilizes an alternative sphingosine kinase-1-mediated pathway to inhibit PP2A and that FTY720-P, acting as a sphingosine-1-phosphate-receptor-1 agonist, elicits signals leading to the Jak2-PI-3Kγ-PKC-SET-mediated PP2A inhibition. Thus, PADs (eg, FTY720) represent suitable therapeutic alternatives for Jak2(V617F) MPNs.
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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.