ArticleBritish journal of haematology2020
Sphingosine kinase-2 is overexpressed in large granular lymphocyte leukaemia and promotes survival through Mcl-1.
Article in British journal of haematology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed, 30 citations in OpenAlex.
- Therapeutic potential of the sphingosine kinase 2 inhibitor opaganib.Pharmaceutical science advances · 2026Review
- Cheminformatics and Machine Learning-Driven QSAR Analysis of SPHK2 Inhibitors for Anticancer Drug Design.Current medicinal chemistry · 2026Article
- Drug Resistance: The Role of Sphingolipid Metabolism.International journal of molecular sciences · 2025Review
- Functional apoptosis profiling reveals vulnerabilities in T-cell large granular lymphocytic leukemia.Annals of hematology · 2025Article
- The Drug Transporter P-Glycoprotein and Its Impact on Ceramide Metabolism-An Unconventional Ally in Cancer Treatment.International journal of molecular sciences · 2024Review
- Signaling controversy and future therapeutical perspectives of targeting sphingolipid network in cancer immune editing and resistance to tumor necrosis factor-α immunotherapy.Cell communication and signaling : CCS · 2024Review
- The emerging roles of sphingosine 1-phosphate and SphK1 in cancer resistance: a promising therapeutic target.Cancer cell international · 2024Review
- Engineered Lipidic Nanomaterials Inspired by Sphingomyelin Metabolism for Cancer Therapy.Molecules (Basel, Switzerland) · 2023Review
- TRIM22 promotes the proliferation of glioblastoma cells by activating MAPK signaling and accelerating the degradation of Raf-1.Experimental & molecular medicine · 2023Article
- Inhibition of Sphingosine Kinase 2 Results in PARK2-Mediated Mitophagy and Induces Apoptosis in Multiple Myeloma.Current oncology (Toronto, Ont.) · 2023Article
- Venetoclax resistance induced by activated T cells can be counteracted by sphingosine kinase inhibitors in chronic lymphocytic leukemia.Frontiers in oncology · 2023Article
- Advancements on the Multifaceted Roles of Sphingolipids in Hematological Malignancies.International journal of molecular sciences · 2022Review
- Synthesis of PP2A-Activating PF-543 Derivatives and Investigation of Their Inhibitory Effects on Pancreatic Cancer Cells.Molecules (Basel, Switzerland) · 2022Article
- Resveratrol triggers anti-proliferative and apoptotic effects in FLT3-ITD-positive acute myeloid leukemia cells via inhibiting ceramide catabolism enzymes.Medical oncology (Northwood, London, England) · 2022Article
- The key role of sphingolipid metabolism in cancer: New therapeutic targets, diagnostic and prognostic values, and anti-tumor immunotherapy resistance.Frontiers in oncology · 2022Review
- Recent Progress in the Development of Opaganib for the Treatment of Covid-19.Drug design, development and therapy · 2022Review
- Pathogenesis and Treatment of T-Large Granular Lymphocytic Leukemia (T-LGLL) in the Setting of Rheumatic Disease.Frontiers in oncology · 2022Review
- Reprogramming lipid metabolism as potential strategy for hematological malignancy therapy.Frontiers in oncology · 2022Review
- Targeting Sphingolipids for Cancer Therapy.Frontiers in oncology · 2021Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Sphingolipid metabolism is increasingly recognised as a therapeutic target in cancer due to its regulation of cell proliferation and apoptosis. The sphingolipid rheostat is proposed to control cell fate through maintaining balance between pro-apoptotic and pro-survival sphingolipids. This balance is regulated by metabolising enzymes involved in sphingolipid production. One such enzyme, sphingosine kinase-2 (SPHK2), produces pro-survival sphingosine 1-phosphate (S1P) by phosphorylation of pro-apoptotic sphingosine. Elevated SPHK2 has been found in multiple cancer types and contributes to cell survival, chemotherapeutic resistance and apoptosis resistance. We have previously shown elevation of S1P in large granular lymphocyte (LGL) leukaemia serum and cells isolated from patients. Here, we examined SPHK2 expression in LGL leukaemia and found SPHK2 mRNA and protein upregulation in a majority of LGL leukaemia patient samples. Knockdown of SPHK2 with siRNA in LGL leukaemia cell lines decreased proliferation. Additionally, the use of ABC294640 or K145, both SPHK2-specific inhibitors, decreased viability of LGL leukaemia cell lines. ABC294640 selectively induced apoptosis in LGL cell lines and freshly isolated LGL leukaemia patient cells compared to normal controls. Mechanistically, SPHK2 inhibition downregulated pro-survival myeloid cell leukaemia-1 (Mcl-1) protein through proteasomal degradation. Targeting of SPHK2 therefore provides a novel therapeutic approach for the treatment of LGL leukaemia.
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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.