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Activated stromal cells transfer mitochondria to rescue acute lymphoblastic leukemia cells from oxidative stress

Overview of attention for article published in Blood, September 2019
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (87th percentile)
  • Good Attention Score compared to outputs of the same age and source (78th percentile)

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20 X users
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2 Facebook pages
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1 Wikipedia page

Citations

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151 Dimensions

Readers on

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155 Mendeley
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Title
Activated stromal cells transfer mitochondria to rescue acute lymphoblastic leukemia cells from oxidative stress
Published in
Blood, September 2019
DOI 10.1182/blood.2019001398
Pubmed ID
Authors

Richard Burt, Aditi Dey, Sarah Aref, Melanie Aguiar, Ayse Akarca, Katharine Bailey, William Day, Steven Hooper, Amy Kirkwood, Kristina Kirschner, Soo-Wah Lee, Cristina Lo Celso, Jiten Manji, Marc R. Mansour, Teresa Marafioti, Rachel J. Mitchell, Robert C. Muirhead, Kenton Cheuk Yan Ng, Constandina Pospori, Ignazio Puccio, Krisztina Zuborne-Alapi, Erik Sahai, Adele K. Fielding

Abstract

We investigated and modelled the mesenchymal stromal cell (MSC) niche in adult acute lymphoblastic leukaemia (ALL). We used gene expression profiling, cytokine/chemokine quantification, flow cytometry and a variety of imaging techniques to show that MSC directly isolated from the primary bone marrow specimens of patients with ALL frequently adopted an activated, cancer-associated fibroblast phenotype. Normal, primary human MSC and the MSC cell line HS27a both became activated de novo, when exposed to the reactive oxygen species (ROS)-inducing chemotherapy agents cytarabine (AraC) and daunorubicin (DNR), a phenomenon blocked by the anti-oxidant N-acetyl cysteine. Chemotherapy-activated HS27a cells were functionally evaluated in a co-culture model with ALL targets. Activated MSC prevented therapy-induced apoptosis and death in ALL targets, via mitochondrial transfer through tunnelling nanotubes (TNT). Reduction of mitochondrial transfer by selective mitochondrial depletion or interference with TNT formation by microtubule inhibitors such as vincristine (VCR) - prevented the 'rescue' function of the activated MSC. Corticosteroids - also a mainstay of ALL therapy - prevented the activation of MSC. We also demonstrated that AraC (but not VCR) - induced activation of MSC, mitochondrial transfer and mitochondrial mass increase in a murine NSG model of disseminated SEM-derived ALL wherein CD19+ cells closely associated with nestin+ MSC after AraC but not the other conditions. Our data propose a readily clinically-exploitable mechanism for improving treatment ALL in which traditional, ROS-inducing chemotherapies are often ineffective at eradicating residual ALL, despite efficiently killing the bulk population.

X Demographics

X Demographics

The data shown below were collected from the profiles of 20 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 155 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 155 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 33 21%
Student > Master 17 11%
Student > Bachelor 16 10%
Researcher 11 7%
Student > Postgraduate 8 5%
Other 18 12%
Unknown 52 34%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 47 30%
Medicine and Dentistry 15 10%
Agricultural and Biological Sciences 10 6%
Immunology and Microbiology 6 4%
Pharmacology, Toxicology and Pharmaceutical Science 4 3%
Other 18 12%
Unknown 55 35%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 17. 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 14 November 2022.
All research outputs
#2,151,621
of 25,024,586 outputs
Outputs from Blood
#2,134
of 33,582 outputs
Outputs of similar age
#43,711
of 347,268 outputs
Outputs of similar age from Blood
#48
of 214 outputs
Altmetric has tracked 25,024,586 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 91st percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 33,582 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.4. This one has done particularly well, scoring higher than 93% 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 347,268 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 87% of its contemporaries.
We're also able to compare this research output to 214 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 78% of its contemporaries.