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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jan 12, 2018 |
| Title |
Targeted inhibition of STAT/TET1 axis as a potent therapeutic strategy for acute myeloid leukemia |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Effective therapy of acute myeloid leukemia (AML) remains an unmet need. DNA methylcytosine dioxygenase Ten-eleven translocation 1 (TET1) is a critical oncoprotein in AML. Through a series of data analysis and drug screening, we identified two compounds (i.e., NSC-311068 and NSC-370284) that selectively suppress TET1 transcription and 5-hydroxymethylcytosine (5hmC) modification, and effectively inhibit cell viability in AML with high level expression of TET1 (i.e., TET1-high AML), including AML carrying t(11q23)/MLL-rearrangements and t(8;21) AML. NSC-311068 and especially NSC-370284 significantly repressed TET1-high AML progression in vivo. UC-514321, a structural analog of NSC-370284, exhibited a more potent therapeutic effect and prolonged the median survival of TET1-high AML mice over three folds. NSC-370284 and UC-514321 both directly target STAT3/5, transcriptional activators of TET1, and thus repress TET1 expression. They also exhibit strong synergistic effects with standard chemotherapy. Our results highlight the therapeutic potential of targeting the STAT/TET1 axis by selective inhibitors in AML treatment.
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| Overall design |
To assess the influence of NSC-370284 on gene expression pattern, we treated THP-1 cells with 50 nM NSC-370284 or DMSO control. RNA samples were collected after 24 hours of treatment. RNA sequencing was performed.
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| Contributor(s) |
Jiang X, Ferchen K, He C, Chen J |
| Citation(s) |
29235481 |
| Submission date |
Jul 14, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
linjian xia |
| E-mail(s) |
xia17720507672@gmail.com
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| Phone |
17720507672
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| Organization name |
wuhan University
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| Street address |
wuhan
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| City |
wuhan |
| ZIP/Postal code |
420000 |
| Country |
China |
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| Platforms (1) |
| GPL15433 |
Illumina HiSeq 1000 (Homo sapiens) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA394528 |
| SRA |
SRP111983 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE101480_Group370_vs_GroupCtrl.all.gene.result.txt.gz |
1.4 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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