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ETV4-Dependent Transcriptional Plasticity Maintains MYC Expression and Results in IMiD Resistance in Multiple Myeloma

Overview of attention for article published in Blood Cancer Discovery, November 2023
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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 (89th percentile)
  • Good Attention Score compared to outputs of the same age and source (75th percentile)

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22 X users

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Title
ETV4-Dependent Transcriptional Plasticity Maintains MYC Expression and Results in IMiD Resistance in Multiple Myeloma
Published in
Blood Cancer Discovery, November 2023
DOI 10.1158/2643-3230.bcd-23-0061
Pubmed ID
Authors

Paola Neri, Benjamin G. Barwick, David Jung, Jonathan C. Patton, Ranjan Maity, Ines Tagoug, Caleb K. Stein, Remi Tilmont, Noemie Leblay, Sungwoo Ahn, Holly Lee, Seth J. Welsh, Daniel L. Riggs, Nicholas Stong, Erin Flynt, Anjan Thakurta, Jonathan J. Keats, Sagar Lonial, P. Leif Bergsagel, Lawrence H. Boise, Nizar J. Bahlis

Abstract

Immunomodulatory Drugs (IMiDs) are a backbone therapy for multiple myeloma (MM). Despite their efficacy, most patients develop resistance, and the mechanism(s) are not fully defined. Here, we show that IMiD responses are directed by IMiD-dependent degradation of IKZF1 and IKZF3 that bind to enhancers necessary to sustain the expression of MYC and other myeloma oncogenes. IMiD treatment universally depleted chromatin-bound IKZF1, but eviction of P300 and BRD4 co-activators only occurred in IMiD-sensitive cells. IKZF1-bound enhancers overlapped other transcription factor-binding motifs, including ETV4. ChIP-seq showed that ETV4 bound to the same enhancers as IKZF1, and ETV4 CRISPR/Cas9-mediated ablation resulted in sensitization of IMiD-resistant MM. ETV4 expression is associated with IMiD resistance in cell lines, poor prognosis in patients, and upregulated at relapse. These data indicate that ETV4 alleviates IKZF1 and IKZF3 dependency in MM by maintaining oncogenic enhancer activity and identify transcriptional plasticity as a previously unrecognized mechanism of IMiD resistance.

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The data shown below were collected from the profiles of 22 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 2 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 2 100%

Demographic breakdown

Readers by professional status Count As %
Librarian 1 50%
Researcher 1 50%
Readers by discipline Count As %
Medicine and Dentistry 2 100%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 15. 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 23 January 2024.
All research outputs
#2,409,837
of 25,376,589 outputs
Outputs from Blood Cancer Discovery
#92
of 208 outputs
Outputs of similar age
#38,149
of 354,220 outputs
Outputs of similar age from Blood Cancer Discovery
#4
of 12 outputs
Altmetric has tracked 25,376,589 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 90th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 208 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 28.5. This one has gotten more attention than average, scoring higher than 56% 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 354,220 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 89% of its contemporaries.
We're also able to compare this research output to 12 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 75% of its contemporaries.