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Direct and Indirect Targets of the E2A-PBX1 Leukemia-Specific Fusion Protein

Overview of attention for article published in PLOS ONE, February 2014
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Title
Direct and Indirect Targets of the E2A-PBX1 Leukemia-Specific Fusion Protein
Published in
PLOS ONE, February 2014
DOI 10.1371/journal.pone.0087602
Pubmed ID
Authors

Christofer Diakos, Yuanyuan Xiao, Shichun Zheng, Leo Kager, Michael Dworzak, Joseph L. Wiemels

Abstract

E2A-PBX1 is expressed as a result of the t(1;19) chromosomal translocation in nearly 5% of cases of childhood acute lymphoblastic leukemia. The E2A-PBX1 chimeric transcription factor contains the N-terminal transactivation domain of E2A (TCF3) fused to the C-terminal DNA-binding homeodomain of PBX1. While there is no doubt of its oncogenic potential, the mechanisms of E2A-PBX1-mediated pre-B cell transformation and the nature of direct E2A-PBX1 target genes and pathways remain largely unknown. Herein we used chromatin immunoprecipitation assays (ChIP-chip) to identify direct targets of E2A-PBX1, and we used gene expression arrays of siRNA E2A-PBX1-silenced cells to evaluate changes in expression induced by the fusion protein. Combined ChIP-chip and expression data analysis gave rise to direct and functional targets of E2A-PBX1. Further we observe that the set of ChIP-chip identified E2A-PBX1 targets show a collective down-regulation trend in the E2A-PBX1 silenced samples compared to controls suggesting an activating role of this fusion transcription factor. Our data suggest that the expression of the E2A-PBX1 fusion gene interferes with key regulatory pathways and functions of hematopoietic biology. Among these are members of the WNT and apoptosis/cell cycle control pathways, and thus may comprise an essential driving force for the propagation and maintenance of the leukemic phenotype. These findings may also provide evidence of potentially attractive therapeutic targets.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 44 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Czechia 3 7%
Germany 1 2%
Unknown 40 91%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 10 23%
Researcher 8 18%
Student > Master 7 16%
Student > Bachelor 5 11%
Other 3 7%
Other 6 14%
Unknown 5 11%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 14 32%
Medicine and Dentistry 11 25%
Agricultural and Biological Sciences 9 20%
Immunology and Microbiology 2 5%
Computer Science 1 2%
Other 2 5%
Unknown 5 11%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 12 February 2014.
All research outputs
#14,189,417
of 22,743,667 outputs
Outputs from PLOS ONE
#116,113
of 194,093 outputs
Outputs of similar age
#172,687
of 307,195 outputs
Outputs of similar age from PLOS ONE
#3,181
of 5,654 outputs
Altmetric has tracked 22,743,667 research outputs across all sources so far. This one is in the 35th percentile – i.e., 35% of other outputs scored the same or lower than it.
So far Altmetric has tracked 194,093 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.1. This one is in the 36th percentile – i.e., 36% 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 307,195 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 41st percentile – i.e., 41% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 5,654 others from the same source and published within six weeks on either side of this one. This one is in the 40th percentile – i.e., 40% of its contemporaries scored the same or lower than it.