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@ARTICLE{Sonnet:128362,
author = {M. Sonnet$^*$ and R. Claus and N. Becker$^*$ and M.
Zucknick$^*$ and J. Petersen$^*$ and D. Lipka$^*$ and C. C.
Oakes$^*$ and M. Andrulis and A. Lier$^*$ and M. Milsom$^*$
and T. Witte$^*$ and L. Gu$^*$ and S.-Z. Kim-Wanner$^*$ and
P. Schirmacher and M. Wulfert and N. Gattermann and M.
Lübbert and F. Rosenbauer and M. Rehli and L. Bullinger and
D. Weichenhan$^*$ and C. Plass$^*$},
title = {{E}arly aberrant {DNA} methylation events in a mouse model
of acute myeloid leukemia.},
journal = {Genome medicine},
volume = {6},
number = {4},
issn = {1756-994X},
address = {London},
publisher = {BioMed Central},
reportid = {DKFZ-2017-04379},
pages = {34},
year = {2014},
abstract = {Aberrant DNA methylation is frequently found in human
malignancies including acute myeloid leukemia (AML). While
most studies focus on later disease stages, the onset of
aberrant DNA methylation events and their dynamics during
leukemic progression are largely unknown.We screened
genome-wide for aberrant CpG island methylation in three
disease stages of a murine AML model that is driven by
hypomorphic expression of the hematopoietic transcription
factor PU.1. DNA methylation levels of selected genes were
correlated with methylation levels of CD34+ cells and
lineage negative, CD127-, c-Kit+, Sca-1+ cells; common
myeloid progenitors; granulocyte-macrophage progenitors; and
megakaryocyte-erythroid progenitors.We identified 1,184
hypermethylated array probes covering 762 associated genes
in the preleukemic stage. During disease progression, the
number of hypermethylated genes increased to 5,465 in the
late leukemic disease stage. Using publicly available data,
we found a significant enrichment of PU.1 binding sites in
the preleukemic hypermethylated genes, suggesting that
shortage of PU.1 makes PU.1 binding sites in the DNA
accessible for aberrant methylation. Many known AML
associated genes such as RUNX1 and HIC1 were found among the
preleukemic hypermethylated genes. Nine novel
hypermethylated genes, FZD5, FZD8, PRDM16, ROBO3, CXCL14,
BCOR, ITPKA, HES6 and TAL1, the latter four being potential
PU.1 targets, were confirmed to be hypermethylated in human
normal karyotype AML patients, underscoring the relevance of
the mouse model for human AML.Our study identified early
aberrantly methylated genes as potential contributors to
onset and progression of AML.},
cin = {C010 / C060 / W190 / V960 / A012 / A010},
ddc = {610},
cid = {I:(DE-He78)C010-20160331 / I:(DE-He78)C060-20160331 /
I:(DE-He78)W190-20160331 / I:(DE-He78)V960-20160331 /
I:(DE-He78)A012-20160331 / I:(DE-He78)A010-20160331},
pnm = {313 - Cancer risk factors and prevention (POF3-313)},
pid = {G:(DE-HGF)POF3-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:24944583},
pmc = {pmc:PMC4062060},
doi = {10.1186/gm551},
url = {https://inrepo02.dkfz.de/record/128362},
}