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Identification of a nucleoside analog active against adenosine kinase–expressing plasma cell malignancies

Overview of attention for article published in Journal of Clinical Investigation, May 2017
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (93rd percentile)
  • Good Attention Score compared to outputs of the same age and source (71st percentile)

Mentioned by

news
4 news outlets
blogs
1 blog
twitter
11 X users
facebook
1 Facebook page

Citations

dimensions_citation
7 Dimensions

Readers on

mendeley
25 Mendeley
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Title
Identification of a nucleoside analog active against adenosine kinase–expressing plasma cell malignancies
Published in
Journal of Clinical Investigation, May 2017
DOI 10.1172/jci83936
Pubmed ID
Authors

Utthara Nayar, Jouliana Sadek, Jonathan Reichel, Denise Hernandez-Hopkins, Gunkut Akar, Peter J. Barelli, Michelle A. Sahai, Hufeng Zhou, Jennifer Totonchy, David Jayabalan, Ruben Niesvizky, Ilaria Guasparri, Duane Hassane, Yifang Liu, Shizuko Sei, Robert H. Shoemaker, J. David Warren, Olivier Elemento, Kenneth M. Kaye, Ethel Cesarman

Abstract

Primary effusion lymphoma (PEL) is a largely incurable malignancy of B cell origin with plasmacytic differentiation. Here, we report the identification of a highly effective inhibitor of PEL. This compound, 6-ethylthioinosine (6-ETI), is a nucleoside analog with toxicity to PEL in vitro and in vivo, but not to other lymphoma cell lines tested. We developed and performed resistome analysis, an unbiased approach based on RNA sequencing of resistant subclones, to discover the molecular mechanisms of sensitivity. We found different adenosine kinase-inactivating (ADK-inactivating) alterations in all resistant clones and determined that ADK is required to phosphorylate and activate 6-ETI. Further, we observed that 6-ETI induces ATP depletion and cell death accompanied by S phase arrest and DNA damage only in ADK-expressing cells. Immunohistochemistry for ADK served as a biomarker approach to identify 6-ETI-sensitive tumors, which we documented for other lymphoid malignancies with plasmacytic features. Notably, multiple myeloma (MM) expresses high levels of ADK, and 6-ETI was toxic to MM cell lines and primary specimens and had a robust antitumor effect in a disseminated MM mouse model. Several nucleoside analogs are effective in treating leukemias and T cell lymphomas, and 6-ETI may fill this niche for the treatment of PEL, plasmablastic lymphoma, MM, and other ADK-expressing cancers.

X Demographics

X Demographics

The data shown below were collected from the profiles of 11 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 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 %
Researcher 3 12%
Other 3 12%
Student > Bachelor 2 8%
Student > Doctoral Student 2 8%
Student > Ph. D. Student 2 8%
Other 5 20%
Unknown 8 32%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 7 28%
Medicine and Dentistry 4 16%
Immunology and Microbiology 1 4%
Nursing and Health Professions 1 4%
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 39. 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 May 2020.
All research outputs
#986,418
of 24,411,829 outputs
Outputs from Journal of Clinical Investigation
#1,237
of 16,841 outputs
Outputs of similar age
#20,428
of 313,897 outputs
Outputs of similar age from Journal of Clinical Investigation
#34
of 115 outputs
Altmetric has tracked 24,411,829 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 16,841 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 16.5. This one has done particularly well, scoring higher than 92% 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 313,897 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 115 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 71% of its contemporaries.