| Title |
Quantitative proteomic analysis of histone modifications in decitabine sensitive and resistant leukemia cell lines
|
|---|---|
| Published in |
Clinical Proteomics, July 2016
|
| DOI | 10.1186/s12014-016-9115-z |
| Pubmed ID | |
| Authors |
Chunchao Zhang, Jinfeng Suo, Hiroyuki Katayama, Yue Wei, Guillermo Garcia-Manero, Samir Hanash |
| Abstract |
The refractory nature of many cancers remains the main health challenge over the past century. The epigenetic drug, decitabine (DAC), represents one of the most promising therapeutic agents in cancers particularly in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). However, its ambiguous anti-tumor mechanism and the unpredictable drug-resistant nature in some population compromise its application in cancer therapy. In crosstalk with DNA methylation, histone post-translational modifications (PTMs) are the key players in modulating the downstream epigenetic status of tumor suppressor genes. This study targets the role of decitabine in epigenetic regulation in leukemia therapy and searches responsive predictors and therapeutic targets for pretreatment evaluation and drug development. A simple, fast, and robust proteomic strategy identified 15 novel PTMs and 60 PTM combinations in two leukemia cell lines (MDS-L and TF-1). Histone modification profiles have been generated and compared between DAC sensitive and resistant groups (n = 3) in response to DAC treatment. Among these histone PTMs, five of which were found differentially upon DAC treatment in drug sensitive and resistant cells: H3.3K36me3, H4K8acK12acK16ac in MDS-L cells; and H3.1K27me1, H3.1K36me1, H3.1K27me1K36me1 in TF-1 cells. They may serve as biomarkers in predicting leukemia and drug responsiveness. In addition, we also explored PTM differences in two cell lines which were developed from early and advanced stages of AML. Three PTMs (H3.1K27me3, H3.1K27me2K36me2 and H3.3K27me2K36me2) are highly abundant in TF-1 cells (advanced AML cell line), suggesting their relevance to leukemogenesis. Our method allowed deep analysis of histone proteins and elucidation of a large number of histone PTMs with high precision and sensitivity. DAC-induced DNA hypomethylation has wide impact on chromatin modifications. This study represents first effort to investigate the undefined epigenetic mechanism of decitabine in leukemia therapy. The identification of 15 novel PTMs and the discovery of several marks have relevance to epigenetic directed therapies. |
X Demographics
The data shown below were collected from the profiles of 5 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| France | 1 | 20% |
| Germany | 1 | 20% |
| Unknown | 3 | 60% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 5 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 22 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 22 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 7 | 32% |
| Student > Bachelor | 3 | 14% |
| Researcher | 3 | 14% |
| Student > Doctoral Student | 2 | 9% |
| Student > Ph. D. Student | 1 | 5% |
| Other | 1 | 5% |
| Unknown | 5 | 23% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 8 | 36% |
| Medicine and Dentistry | 3 | 14% |
| Agricultural and Biological Sciences | 2 | 9% |
| Mathematics | 1 | 5% |
| Immunology and Microbiology | 1 | 5% |
| Other | 3 | 14% |
| Unknown | 4 | 18% |
Attention Score in Context
This research output has an Altmetric Attention Score of 5. 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 15 June 2023.
All research outputs
#6,477,117
of 24,041,016 outputs
Outputs from Clinical Proteomics
#76
of 298 outputs
Outputs of similar age
#103,858
of 361,320 outputs
Outputs of similar age from Clinical Proteomics
#1
of 6 outputs
Altmetric has tracked 24,041,016 research outputs across all sources so far. This one has received more attention than most of these and is in the 72nd percentile.
So far Altmetric has tracked 298 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.1. This one has gotten more attention than average, scoring higher than 73% 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 361,320 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 71% of its contemporaries.
We're also able to compare this research output to 6 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them