Evidence map›Paper›PMID 31097785›Full record

ArticleLeukemia2019

Sphingosine-1-phosphate signalling drives an angiogenic transcriptional programme in diffuse large B cell lymphoma.

Lauren Lupino, Tracey Perry, Sandra Margielewska, Robert Hollows, Maha Ibrahim, Matthew Care, Jeremy Allegood, Reuben Tooze, Roger Sabbadini, Gary Reynolds and 11 more

Open access · hybridAbstract read
In one paragraph

Article in Leukemia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
1.9field-weighted citation impact, top 14% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.

  1. Pooled it
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  6. Targeting sphingosine kinase 1 in p53KO thymic lymphoma.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors at 10 institutions in 4 countries.

Lauren LupinoInstitute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.
Tracey PerryInstitute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.
Sandra MargielewskaInstitute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.
Robert HollowsInstitute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.
Maha IbrahimInstitute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.
Matthew CareSection of Experimental Haematology, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.ORCID http://orcid.org/0000-0001-6584-5889
Jeremy AllegoodDepartment of Biochemistry and Molecular Biology and Massey Cancer, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Reuben ToozeSection of Experimental Haematology, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
Roger SabbadiniDepartment of Biology, San Diego State University, San Diego, CA, USA.
Gary ReynoldsInstitute of Immunology & Immunotherapy, University of Birmingham, Birmingham, UK.ORCID http://orcid.org/0000-0002-3250-0582
Roy BicknellInstitutes of Cardiovascular Sciences and Biomedical Research, University of Birmingham, Birmingham, UK.
Zbigniew RudzkiDepartment of Histopathology, Heartlands Hospital, Birmingham, UK.
Ye Lin HockDepartment of Histopathology, Walsall Manor Hospital, Walsall, UK.
Ulises ZanettoDepartment of Histopathology, City Hospital, Birmingham, UK.
Wenbin WeiInstitute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.ORCID http://orcid.org/0000-0003-1288-6999
William SimmonsInstitute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.
Sarah SpiegelDepartment of Biochemistry and Molecular Biology and Massey Cancer, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Ciaran B J WoodmanInstitute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.
Martin RoweInstitute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.
Katerina VrzalikovaInstitute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK. k.vrzalikova@bham.ac.uk.
Paul G MurrayInstitute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK. p.g.murray@bham.ac.uk.
University of Birmingham · GBUniversity of Leeds · GBVirginia Commonwealth University · USBirmingham City Hospital · GBCancer Research UK Clinical Trials Unit · GBHeartlands Hospital · GBInstitute of Molecular and Translational Medicine · CZNIHR Birmingham Biomedical Research Centre · GBSan Diego State University · USWalsall Manor Hospital · GB

Funding

SPHINGOSINE AS A MODULATOR OF CELLULAR PROLIFERATIONR01GM043880 · NIGMS · VIRGINIA COMMONWEALTH UNIVERSITY · PI SPIEGEL, SARAH · 1990 to 2023
$3.8M
Cancer Research UK 10066Cancer Research UK (CRUK) C7845/A17723NIGMS NIH HHS R01 GM043880
6 · The paper itself

Abstract

Although the over-expression of angiogenic factors is reported in diffuse large B-cell lymphoma (DLBCL), the poor response to anti-VEGF drugs observed in clinical trials suggests that angiogenesis in these tumours might be driven by VEGF-independent pathways. We show that sphingosine kinase-1 (SPHK1), which generates the potent bioactive sphingolipid sphingosine-1-phosphate (S1P), is over-expressed in DLBCL. A meta-analysis of over 2000 cases revealed that genes correlated with SPHK1 mRNA expression in DLBCL were significantly enriched for tumour angiogenesis meta-signature genes; an effect evident in both major cell of origin (COO) and stromal subtypes. Moreover, we found that S1P induces angiogenic signalling and a gene expression programme that is present within the tumour vasculature of SPHK1-expressing DLBCL. Importantly, S1PR1 functional antagonists, including Siponimod, and the S1P neutralising antibody, Sphingomab, inhibited S1P signalling in DLBCL cells in vitro. Furthermore, Siponimod, also reduced angiogenesis and tumour growth in an S1P-producing mouse model of angiogenic DLBCL. Our data define a potential role for S1P signalling in driving an angiogenic gene expression programme in the tumour vasculature of DLBCL and suggest novel opportunities to target S1P-mediated angiogenesis in patients with DLBCL.

Indexed as

Signal TransductionTranscriptomeAnimalsCell Line, TumorComputational BiologyDisease Models, AnimalEndothelial CellsGene Expression Regulation, NeoplasticHumansImmunohistochemistryLymphoma, Large B-Cell, DiffuseLysophospholipidsMiceNeovascularization, PathologicRNA, MessengerSphingosineLysophospholipidsRNA, MessengerSphingosinesphingosine 1-phosphate

Identifiers

PMID31097785
PMCPMC6887546
OpenAlexW2944870904

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.