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X Demographics
Mendeley readers
Attention Score in Context
| Title |
CCL2 is a KIT D816V–dependent modulator of the bone marrow microenvironment in systemic mastocytosis
|
|---|---|
| Published in |
Blood, November 2016
|
| DOI | 10.1182/blood-2016-09-739003 |
| Pubmed ID | |
| Authors |
Georg Greiner, Nadine Witzeneder, Angelika Berger, Klaus Schmetterer, Gregor Eisenwort, Ana-Iris Schiefer, Simone Roos, Theresia Popow-Kraupp, Leonhard Müllauer, Johannes Zuber, Veronika Sexl, Lukas Kenner, Wolfgang R Sperr, Peter Valent, Matthias Mayerhofer, Gregor Hoermann |
| Abstract |
Systemic mastocytosis (SM) is characterized by abnormal accumulation of neoplastic mast cells harboring the activating KIT mutation D816V in the bone marrow and other internal organs. Similar to other myeloproliferative neoplasms, increased production of pro-fibrogenic and angiogenic cytokines and related alterations of the bone marrow microenvironment are commonly found in SM. However, only little is known about mechanisms and effector molecules triggering fibrosis and angiogenesis in SM. Here we show that KIT D816V promotes expression of the pro-angiogenic cytokine CCL-2 in neoplastic mast cells. Correspondingly, the KIT-targeting drug midostaurin and RNAi-mediated knockdown of KIT reduced expression of CCL-2. We also found that NFκB contributes to KIT-dependent upregulation of CCL-2 in mast cells. In addition, CCL-2 secreted by KIT D816V+ mast cells was found to promote the migration of human endothelial cells in vitro Furthermore, knockdown of CCL-2 in neoplastic mast cells resulted in reduced microvessel density and reduced tumor growth in NSG mice in vivo, compared to CCL-2-expressing cells. Finally, we measured CCL-2 serum concentrations in patients with SM and found that CCL-2 levels were significantly elevated in mastocytosis patients compared to controls. Furthermore, CCL-2 serum levels were higher in patients with advanced SM and were found to correlate with poor survival. In summary, we have identified CCL-2 as a novel, KIT D816V-dependent, key regulator of vascular cell migration and angiogenesis in SM. CCL-2 expression correlates with disease severity and prognosis. Whether CCL-2 may serve as a therapeutic target in advanced SM remains to be determined in forthcoming studies. |
X Demographics
The data shown below were collected from the profiles of 9 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 3 | 33% |
| Austria | 1 | 11% |
| Unknown | 5 | 56% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 33% |
| Scientists | 2 | 22% |
| Science communicators (journalists, bloggers, editors) | 2 | 22% |
| Practitioners (doctors, other healthcare professionals) | 2 | 22% |
Mendeley readers
The data shown below were compiled from readership statistics for 37 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 3% |
| Brazil | 1 | 3% |
| Unknown | 35 | 95% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 9 | 24% |
| Student > Ph. D. Student | 6 | 16% |
| Other | 3 | 8% |
| Student > Master | 3 | 8% |
| Student > Bachelor | 2 | 5% |
| Other | 7 | 19% |
| Unknown | 7 | 19% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 11 | 30% |
| Medicine and Dentistry | 6 | 16% |
| Agricultural and Biological Sciences | 4 | 11% |
| Immunology and Microbiology | 3 | 8% |
| Computer Science | 1 | 3% |
| Other | 2 | 5% |
| Unknown | 10 | 27% |
Attention Score in Context
This research output has an Altmetric Attention Score of 37. 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 01 September 2022.
All research outputs
#1,098,555
of 25,377,790 outputs
Outputs from Blood
#806
of 33,240 outputs
Outputs of similar age
#18,771
of 288,247 outputs
Outputs of similar age from Blood
#36
of 778 outputs
Altmetric has tracked 25,377,790 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 95th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 33,240 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.6. This one has done particularly well, scoring higher than 97% of its peers.
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 288,247 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 93% of its contemporaries.
We're also able to compare this research output to 778 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 95% of its contemporaries.