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| Status |
Public on Apr 30, 2017 |
| Title |
Epigenetic minicircuitry of AML1-ETO/THAP10/MIR383 contributes t(8;21) AML leukemogenesis |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by array
Methylation profiling by genome tiling array
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| Summary |
AML1-ETO is regarded as an initial event and plays a pivotal role in t(8;21) acute myeloid leukemia (AML) which is a highly heterogeneous disease. DNA methylation patterns are frequently deregulated in t(8;21) AML, though little is known of the mechanisms through which specific gene sets become aberrantly methylated. Here, We found that the promoter DNA methylation signature of t(8;21) AML blasts differs from those of normal CD34+ bone marrow cells and other AMLs. This signature contains 408 differentially methylated genes, many of which are genes involved in cancer pathway and myeloid leukemia. Database systematic survey and differential methylated regions (DMR) analysis were performed. These study demonstrated that a novel hypermethylated zinc finger containing protein-THAP10 is a target gene and can be epigenetic silenced by AML1-ETO at transcriptional level in t(8;21) AML and silencing of THAP10 by AML1-ETO predicts a poor clinical outcome. Our findings also identified that THAP10 is a bona fide target of miR-383 which can be epigenetic activated by AML1-ETO. In this study, we provided evidence that epigenetic silencing of THAP10 is the mechanistic link between AML1-ETO fusion proteins and tyrosine kinase cascades. In addition, we showed that THAP10 is a nuclear protein which inhibits myeloid proliferation inhibition and promotes differentiation both in vitro and in vivo. Altogether, our results revealed an unexpected and important link between fusion protein AML1-ETO, mir-383, THAP10 and tyrosine cascades in t(8;21) AML.
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| Overall design |
Bisulphite converted DNA from the 12 samples were hybridised to the Illumina HumanMethylation450 BeadChip, including 5 t(8;21)-positive AML, 5 t(8;21)-negative AML M2 subtype according FAB and 2 normal bone marrow.
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| Contributor(s) |
Li Y, Shi J |
| Citation missing |
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| |
| Submission date |
Apr 21, 2016 |
| Last update date |
Mar 22, 2019 |
| Contact name |
Shi Long |
| E-mail(s) |
csjl@sohu.com
|
| Phone |
1012347654
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| Organization name |
NDUT
|
| Street address |
Road One
|
| City |
Beijing |
| State/province |
Peking |
| ZIP/Postal code |
100000 |
| Country |
China |
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| Platforms (1) |
| GPL13534 |
Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA319156 |
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