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Retinoic acid synergizes with the unfolded protein response and oxidative stress to induce cell death in FLT3-ITD+ AML

Overview of attention for article published in Blood Advances, December 2019
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (81st percentile)
  • Good Attention Score compared to outputs of the same age and source (79th percentile)

Mentioned by

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3 X users
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2 patents

Citations

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22 Dimensions

Readers on

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27 Mendeley
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Title
Retinoic acid synergizes with the unfolded protein response and oxidative stress to induce cell death in FLT3-ITD+ AML
Published in
Blood Advances, December 2019
DOI 10.1182/bloodadvances.2019000540
Pubmed ID
Authors

Silvia Masciarelli, Ernestina Capuano, Tiziana Ottone, Mariadomenica Divona, Serena Lavorgna, Francesca Liccardo, Martyna Śniegocka, Serena Travaglini, Nelida I. Noguera, Alessandra Picardi, Vincenzo Petrozza, Alessandro Fatica, Luca Tamagnone, Maria Teresa Voso, Francesco Lo Coco, Francesco Fazi

Abstract

Acute myeloid leukemia (AML) is often characterized by the expression of fusion or mutant proteins that cause impaired differentiation and enhanced proliferation and survival. The presence of mutant proteins prone to misfolding can render the cells sensitive to endoplasmic reticulum (ER) stress and oxidative stress that could otherwise be overcome. Here, we show that the triple combination of the differentiating agent retinoic acid (RA), the ER stress-inducing drug tunicamycin (Tm), and arsenic trioxide (ATO), able to generate oxidative stress, leads to the death of AML cell lines expressing fusion proteins involving the gene MLL and the internal tandem duplication (ITD) in the FLT3 tyrosine kinase receptor. Importantly, the combination of RA, Tm, and ATO decreased the colony-forming capacity of primary leukemic blasts bearing the FLT-ITD mutation without affecting healthy hematopoietic progenitor cells. We demonstrate in cell lines that combination of these drugs generates ER and oxidative stresses and impairs maturation and causes accumulation of FLT3 protein in the ER. Our data provide a proof of concept that low amounts of drugs that generate ER and oxidative stresses combined with RA could be an effective targeted therapy to hit AML cells characterized by MLL fusion proteins and FLT3-ITD mutation.

X Demographics

X Demographics

The data shown below were collected from the profiles of 3 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 27 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 27 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 6 22%
Student > Ph. D. Student 5 19%
Professor > Associate Professor 4 15%
Student > Bachelor 3 11%
Professor 2 7%
Other 4 15%
Unknown 3 11%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 9 33%
Medicine and Dentistry 6 22%
Environmental Science 1 4%
Agricultural and Biological Sciences 1 4%
Nursing and Health Professions 1 4%
Other 2 7%
Unknown 7 26%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 9. 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 05 August 2021.
All research outputs
#3,343,860
of 23,182,015 outputs
Outputs from Blood Advances
#707
of 2,736 outputs
Outputs of similar age
#81,867
of 459,344 outputs
Outputs of similar age from Blood Advances
#23
of 110 outputs
Altmetric has tracked 23,182,015 research outputs across all sources so far. Compared to these this one has done well and is in the 84th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,736 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 11.4. This one has gotten more attention than average, scoring higher than 74% 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 459,344 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 81% of its contemporaries.
We're also able to compare this research output to 110 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 79% of its contemporaries.