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| Status |
Public on Aug 19, 2013 |
| Title |
Epigenetic changes in Down syndrome leukemogenesis |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Methylation profiling by genome tiling array
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| Summary |
Acute megakaryoblastic leukemia (AMKL) is more frequently seen in Down syndrome patients, where it is often preceded by a transient myeloproliferative disorder (DS-TMD). The development of DS-TMD and DS-AMKL require not only the presence of the trisomy 21 but also that of GATA1 mutations. However, despite extensive studies into the genetics of DS-AMKL, not much is known about the epigenetic deregulation associated with this disease. In order to understand how epigenetic changes at the DNA methylation level contribute to DS leukemogenesis we performed DNA methylation profiling at different stages of development of this disease and analyzed the dynamics of epigenetic reprogramming. Early genome-wide epigenetic changes can be detected in trisomy 21 fetal liver mononuclear cells, even prior to the development of hematological abnormalities. These early changes are characterized by marked loss of DNA methylation at genes associated with regulation of key developmental processes. This first wave of aberrant DNA hypomethylation is followed by a second wave of epigenetic reprogramming detected in blast cells from DS-TMD and DS-AMKL, characterized by gains of methylation. This second wave of hypermethylation targets a distinct set of genes, preferentially affecting genes involved in hematopoiesis and regulation of cell growth and proliferation.
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| Overall design |
DNA methylation profiles obtained at different stages of the development of Down syndrome AMKL and from CD41+ cells from partial trisomic mice
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| Contributor(s) |
Figueroa ME, Crispino JD |
| Citation(s) |
23980066 |
| |
| Submission date |
Apr 18, 2013 |
| Last update date |
Nov 05, 2013 |
| Contact name |
Maria Eugenia Figueroa |
| E-mail(s) |
mef162@miami.edu
|
| Organization name |
University of Miiami
|
| Department |
Human Genetics
|
| Lab |
Maria Figueroa
|
| Street address |
1501 NW 10th Ave, BRB 709A, Locator code C227
|
| City |
Miami |
| State/province |
FL |
| ZIP/Postal code |
33136 |
| Country |
USA |
| |
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| Platforms (2) |
| GPL17031 |
Nimblegen Human HG19_HELP array [100128_HG19_MKF_HELP_ChIP] |
| GPL17032 |
Nimblegen Mouse MM9_KF_Meth array [100520_MM9_KF_Meth] |
|
| Samples (43)
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| Relations |
| BioProject |
PRJNA197487 |
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