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Series GSE42118 Query DataSets for GSE42118
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
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.
Overall design Bisulphite converted DNA from the 10 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip
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
Organization name Heidelberg University
Lab Molecular Hematology and Oncology
Street address Im Neuenheimer Feld 410
City Heidelberg
ZIP/Postal code 69120
Country Germany
Platforms (1)
GPL13534 Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
Samples (10)
GSM1032763 APL_10325_hm450
GSM1032764 APL_10545_hm450
GSM1032765 APL_11364_hm450
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
BioProject PRJNA179153

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE42118_RAW.tar 183.1 Mb (http)(custom) TAR
GSE42118_all_data_raw.tsv.gz 22.2 Mb (ftp)(http) TSV
Processed data included within Sample table

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