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X Demographics
Mendeley readers
Attention Score in Context
| Title |
SWI/SNF blockade disrupts PU.1-directed enhancer programs in normal hematopoietic cells and acute myeloid leukemia
|
|---|---|
| Published in |
Cancer Research, January 2023
|
| DOI | 10.1158/0008-5472.can-22-2129 |
| Pubmed ID | |
| Authors |
Courtney Chambers, Katerina Cermakova, Yuen San Chan, Kristen Kurtz, Katharina Wohlan, Andrew Henry Lewis, Christiana Wang, Anh Pham, Milan Dejmek, Michal Sala, Mario Loeza Cabrera, Rogelio Aguilar, Radim Nencka, H. Daniel Lacorazza, Rachel E. Rau, H. Courtney Hodges |
| Abstract |
In acute myeloid leukemia (AML), SWI/SNF chromatin remodeling complexes sustain leukemic identity by driving high levels of MYC. Previous studies have implicated the hematopoietic transcription factor PU.1 (SPI1) as an important target of SWI/SNF inhibition, but PU.1 is widely regarded to have pioneer-like activity. As a result, many questions have remained regarding the interplay between PU.1 and SWI/SNF in AML as well as normal hematopoiesis. Here we found that PU.1 binds to most of its targets in a SWI/SNF-independent manner and recruits SWI/SNF to promote accessibility for other AML core regulatory factors, including RUNX1, LMO2, and MEIS1. SWI/SNF inhibition in AML cells reduced DNA accessibility and binding of these factors at PU.1 sites and redistributed PU.1 to promoters. Analysis of non-tumor hematopoietic cells revealed that similar effects also impair PU.1-dependent B cell and monocyte populations. Nevertheless, SWI/SNF inhibition induced profound therapeutic response in an immunocompetent AML mouse model as well as in primary human AML samples. In vivo, SWI/SNF inhibition promoted leukemic differentiation and reduced the leukemic stem cell burden in bone marrow but also induced leukopenia. These results reveal a variable therapeutic window for SWI/SNF blockade in AML and highlight important off-tumor effects of such therapies in immunocompetent settings. |
X Demographics
The data shown below were collected from the profiles of 30 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 10 | 33% |
| United Kingdom | 2 | 7% |
| Netherlands | 1 | 3% |
| India | 1 | 3% |
| Czechia | 1 | 3% |
| Korea, Republic of | 1 | 3% |
| Unknown | 14 | 47% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 15 | 50% |
| Scientists | 13 | 43% |
| Practitioners (doctors, other healthcare professionals) | 2 | 7% |
Mendeley readers
The data shown below were compiled from readership statistics for 26 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 26 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 5 | 19% |
| Researcher | 3 | 12% |
| Unspecified | 2 | 8% |
| Student > Postgraduate | 2 | 8% |
| Professor | 1 | 4% |
| Other | 3 | 12% |
| Unknown | 10 | 38% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 8 | 31% |
| Agricultural and Biological Sciences | 4 | 15% |
| Unspecified | 2 | 8% |
| Medicine and Dentistry | 1 | 4% |
| Unknown | 11 | 42% |
Attention Score in Context
This research output has an Altmetric Attention Score of 135. 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 02 November 2023.
All research outputs
#315,625
of 25,822,778 outputs
Outputs from Cancer Research
#142
of 18,917 outputs
Outputs of similar age
#7,642
of 477,691 outputs
Outputs of similar age from Cancer Research
#2
of 152 outputs
Altmetric has tracked 25,822,778 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 98th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 18,917 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.6. This one has done particularly well, scoring higher than 99% 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 477,691 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 98% of its contemporaries.
We're also able to compare this research output to 152 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 98% of its contemporaries.