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| Status |
Public on Nov 08, 2012 |
| Title |
DNA methylation changes are a late event in Acute Promyelocytic Leukemia and coincide with loss of transcription factor binding (Illumina Methylation) |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by genome tiling array
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| Summary |
The origin of aberrant DNA methylation in cancer remains largely unknown. In this study, we elucidated the DNA methylome in primary Acute Promyelocytic Leukemia (APL) and the role of PML-RARa in establishing these patterns. APL patients showed increased genome-wide DNA methylation with higher variability than healthy CD34+ cells, promyelocytes and remission bone marrow. A core set of differentially methylated regions in APL was identified. Age at diagnosis, Sanz score and Flt3-mutation status characterized methylation subtypes. Transcription factor binding sites, e.g. c-myc binding sites were associated with low methylation. SUZ12 and REST binding sites identified in embryonic stem cells were, however, preferentially DNA hypermethylated in APL. Unexpectedly, PML-RARa binding sites were also protected from aberrant DNA methylation in APL. In line, myeloid cells from pre-leukemic PML-RARa knock-in mice did not show altered DNA methylation and expression of PML-RARa in hematopoietic progenitor cells prevented differentiation without affecting DNA methylation. ATRA treatment of APL blasts did also not result in DNA methylation changes. These results suggest that aberrant DNA methylation is associated with leukemia phenotype but not required for PML-RARa-mediated initiation of leukemogenesis.
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| Overall design |
Bisulphite converted DNA from the 10 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip
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| Contributor(s) |
Rohde C, Schoofs T, Müller-Tidow C |
| Citation(s) |
23152544 |
| Submission date |
Nov 07, 2012 |
| Last update date |
Mar 22, 2019 |
| Contact name |
Christian Rohde |
| E-mail(s) |
christian.rohde@uni-heidelberg.de
|
| Organization name |
Heidelberg University
|
| Lab |
Molecular Hematology and Oncology
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| Street address |
Im Neuenheimer Feld 410
|
| City |
Heidelberg |
| ZIP/Postal code |
69120 |
| Country |
Germany |
| |
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| Platforms (1) |
| GPL13534 |
Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482) |
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| Samples (10)
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| This SubSeries is part of SuperSeries: |
| GSE42119 |
DNA methylation changes are a late event in Acute Promyelocytic Leukemia and coincide with loss of transcription factor binding |
|
| Relations |
| BioProject |
PRJNA179153 |
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