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S1PR1 drives a feedforward signalling loop to regulate BATF3 and the transcriptional programme of Hodgkin lymphoma cells

Overview of attention for article published in Leukemia, September 2017
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Title
S1PR1 drives a feedforward signalling loop to regulate BATF3 and the transcriptional programme of Hodgkin lymphoma cells
Published in
Leukemia, September 2017
DOI 10.1038/leu.2017.275
Pubmed ID
Authors

K Vrzalikova, M Ibrahim, M Vockerodt, T Perry, S Margielewska, L Lupino, E Nagy, E Soilleux, D Liebelt, R Hollows, A Last, G Reynolds, M Abdullah, H Curley, M Care, D Krappmann, R Tooze, J Allegood, S Spiegel, W Wei, C B J Woodman, P G Murray

Abstract

The Hodgkin/Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (HL) are characterised by the aberrant activation of multiple signalling pathways. Here we show that a subset of HL displays altered expression of sphingosine-1-phosphate (S1P) receptors (S1PR). S1P activates phosphatidylinositide 3-kinase (PI3-K) in these cells that is mediated by the increased expression of S1PR1 and the decreased expression of S1PR2. We also showed that genes regulated by PI3-K signalling pathway in HL cell lines significantly overlap with the transcriptional programme of primary HRS cells. Genes up-regulated by the PI3-K pathway included the basic leucine zipper transcription factor, ATF-like 3 (BATF3), which is normally associated with the development of dendritic cells. Immunohistochemistry confirmed that BATF3 was expressed in HRS cells of most HL cases. In contrast, in normal lymphoid tissues, BATF3 expression was confined to a small fraction of CD30-positive immunoblasts. Knockdown of BATF3 in HL cell lines revealed that BATF3 contributed to the transcriptional programme of primary HRS cells, including the upregulation of S1PR1. Our data suggest that disruption of this potentially oncogenic feed-forward S1P signalling loop could provide novel therapeutic opportunities for patients with HL.Leukemia accepted article preview online, 07 September 2017. doi:10.1038/leu.2017.275.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 25 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 25 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 5 20%
Researcher 3 12%
Other 2 8%
Librarian 1 4%
Lecturer 1 4%
Other 4 16%
Unknown 9 36%
Readers by discipline Count As %
Agricultural and Biological Sciences 4 16%
Medicine and Dentistry 4 16%
Biochemistry, Genetics and Molecular Biology 3 12%
Immunology and Microbiology 2 8%
Social Sciences 1 4%
Other 1 4%
Unknown 10 40%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 04 February 2023.
All research outputs
#14,559,218
of 25,307,332 outputs
Outputs from Leukemia
#3,957
of 5,413 outputs
Outputs of similar age
#157,589
of 321,742 outputs
Outputs of similar age from Leukemia
#42
of 66 outputs
Altmetric has tracked 25,307,332 research outputs across all sources so far. This one is in the 41st percentile – i.e., 41% of other outputs scored the same or lower than it.
So far Altmetric has tracked 5,413 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.5. This one is in the 25th percentile – i.e., 25% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 321,742 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 50% of its contemporaries.
We're also able to compare this research output to 66 others from the same source and published within six weeks on either side of this one. This one is in the 37th percentile – i.e., 37% of its contemporaries scored the same or lower than it.