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Pharmacologic Targeting of Chromatin Modulators As Therapeutics of Acute Myeloid Leukemia

Overview of attention for article published in Frontiers in oncology, October 2017
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Title
Pharmacologic Targeting of Chromatin Modulators As Therapeutics of Acute Myeloid Leukemia
Published in
Frontiers in oncology, October 2017
DOI 10.3389/fonc.2017.00241
Pubmed ID
Authors

Rui Lu, Gang Greg Wang

Abstract

Acute myeloid leukemia (AML), a common hematological cancer of myeloid lineage cells, generally exhibits poor prognosis in the clinic and demands new treatment options. Recently, direct sequencing of samples from human AMLs and pre-leukemic diseases has unveiled their mutational landscapes and significantly advanced the molecular understanding of AML pathogenesis. The newly identified recurrent mutations frequently "hit" genes encoding epigenetic modulators, a wide range of chromatin-modifying enzymes and regulatory factors involved in gene expression regulation, supporting aberration of chromatin structure and epigenetic modification as a main oncogenic mechanism and cancer-initiating event. Increasing body of evidence demonstrates that chromatin modification aberrations underlying the formation of blood cancer can be reversed by pharmacological targeting of the responsible epigenetic modulators, thus providing new mechanism-based treatment strategies. Here, we summarize recent advances in development of small-molecule inhibitors specific to chromatin factors and their potential applications in the treatment of genetically defined AMLs. These compounds selectively inhibit various subclasses of "epigenetic writers" (such as histone methyltransferases MLL/KMT2A, G9A/KMT1C, EZH2/KMT6A, DOT1L/KMT4, and PRMT1), "epigenetic readers" (such as BRD4 and plant homeodomain finger proteins), and "epigenetic erasers" (such as histone demethylases LSD1/KDM1A and JMJD2C/KDM4C). We also discuss about the molecular mechanisms underpinning therapeutic effect of these epigenetic compounds in AML and favor their potential usage for combinational therapy and treatment of pre-leukemia diseases.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 60 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 60 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 11 18%
Student > Ph. D. Student 9 15%
Student > Bachelor 9 15%
Student > Doctoral Student 5 8%
Student > Master 5 8%
Other 9 15%
Unknown 12 20%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 22 37%
Agricultural and Biological Sciences 11 18%
Medicine and Dentistry 6 10%
Pharmacology, Toxicology and Pharmaceutical Science 3 5%
Immunology and Microbiology 2 3%
Other 3 5%
Unknown 13 22%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 October 2017.
All research outputs
#22,764,772
of 25,382,440 outputs
Outputs from Frontiers in oncology
#15,925
of 22,428 outputs
Outputs of similar age
#293,414
of 334,091 outputs
Outputs of similar age from Frontiers in oncology
#74
of 98 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 22,428 research outputs from this source. They receive a mean Attention Score of 3.0. This one is in the 1st percentile – i.e., 1% 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 334,091 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 98 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.