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Transcriptional Plasticity Drives Leukemia Immune Escape

Overview of attention for article published in Blood Cancer Discovery, August 2022
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (77th percentile)
  • Average Attention Score compared to outputs of the same age and source

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Title
Transcriptional Plasticity Drives Leukemia Immune Escape
Published in
Blood Cancer Discovery, August 2022
DOI 10.1158/2643-3230.bcd-21-0207
Pubmed ID
Authors

Kenneth Eagle, Taku Harada, Jérémie Kalfon, Monika W. Perez, Yaser Heshmati, Jazmin Ewers, Jošt Vrabič Koren, Joshua M. Dempster, Guillaume Kugener, Vikram R. Paralkar, Charles Y. Lin, Neekesh V. Dharia, Kimberly Stegmaier, Stuart H. Orkin, Maxim Pimkin

Abstract

Relapse of acute myeloid leukemia (AML) after allogeneic bone marrow transplantation has been linked to immune evasion due to reduced expression of major histocompatibility complex class II (MHC-II) proteins through unknown mechanisms. We developed CORENODE, a computational algorithm for genome-wide transcription network decomposition, that identified a transcription factor (TF) tetrad, consisting of IRF8, MYB, MEF2C and MEIS1, regulating MHC-II expression in AML cells. We show that reduced MHC-II expression at relapse is transcriptionally driven by combinatorial changes in the expression of these TFs, where MYB and IRF8 play major opposing roles, acting independently of the IFN-gamma/CIITA pathway. Beyond the MHC-II genes, MYB and IRF8 antagonistically regulate a broad genetic program responsible for cytokine signaling and T-cell stimulation that displays reduced expression at relapse. A small number of cells with altered TF abundance and silenced MHC-II expression are present at the time of initial leukemia diagnosis, likely contributing to eventual relapse.

Twitter Demographics

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Attention Score in Context

This research output has an Altmetric Attention Score of 8. 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 09 August 2022.
All research outputs
#3,942,673
of 21,815,602 outputs
Outputs from Blood Cancer Discovery
#81
of 143 outputs
Outputs of similar age
#72,829
of 328,714 outputs
Outputs of similar age from Blood Cancer Discovery
#10
of 18 outputs
Altmetric has tracked 21,815,602 research outputs across all sources so far. Compared to these this one has done well and is in the 81st percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 143 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 24.4. This one is in the 43rd percentile – i.e., 43% of its peers scored the same or lower than it.
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 328,714 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 77% of its contemporaries.
We're also able to compare this research output to 18 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 50% of its contemporaries.