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@ARTICLE{Smith:186736,
author = {C. Smith and A. Goyal$^*$ and D. Weichenhan$^*$ and E.
Allemand and A. Mayakonda$^*$ and U. Toprak$^*$ and A.
Riedel$^*$ and E. Balducci and M. Manojkumar$^*$ and A.
Pejkovska$^*$ and O. Mücke$^*$ and E. Sollier$^*$ and A. M.
A. Bakr$^*$ and K. Breuer$^*$ and P. Lutsik$^*$ and O.
Hermine and S. Spicuglia and V. Asnafi and C. Plass$^*$ and
A. Touzart$^*$},
title = {{TAL}1 activation in {T}-{C}ell acute lymphoblastic
leukemia: {A} novel oncogenic 3' neoenhancer.},
journal = {Haematologica},
volume = {108},
number = {5},
issn = {1592-8721},
address = {Pavia},
publisher = {Ferrata Storti Found},
reportid = {DKFZ-2023-00088},
pages = {1259-1271},
year = {2023},
note = {#EA:B370#LA:B370# / 2023 May 1;108(5):1259-1271},
abstract = {T-cell acute lymphocytic leukemia protein 1 (TAL1) is one
of the most frequently deregulated oncogenes in T-cell acute
lymphoblastic leukemia (T-ALL). Its deregulation can occur
through diverse in cis-alterations, including SIL-TAL1
microdeletions, translocations with Tcell Receptor (TCR)
loci and, more recently described upstream intergenic
non-coding mutations. These mutations consist of recurrent
focal microinsertions that create an oncogenic neo-enhancer
accompanied with activating epigenetic marks. This
observation laid the groundwork for an innovative paradigm,
the activation of proto-oncogenes via genomic alterations of
non-coding intergenic regions. However, for the majority of
TAL1 expressing (TAL1+) T-ALLs, the deregulation mechanism
remains 'unresolved'. We took advantage of H3K27ac and
H3K4me3 ChIP-seq data of eight T-ALLs, including five TAL1+
cases and identified a putative novel oncogenic neo-enhancer
downstream of TAL1 in an 'unresolved' monoallelic TAL1+
case. A rare but recurrent somatic heterozygous
microinsertion within this region creates a de novo binding
site for MYB transcription factor (TF). Here, we demonstrate
that this mutation leads to increased enhancer activity,
gain of active epigenetic marks and TAL1 activation via
recruitment of MYB. These results highlight the diversity of
non-coding mutations that can drive oncogene activation.},
cin = {B370 / B087 / HD01},
ddc = {610},
cid = {I:(DE-He78)B370-20160331 / I:(DE-He78)B087-20160331 /
I:(DE-He78)HD01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36632736},
doi = {10.3324/haematol.2022.281583},
url = {https://inrepo02.dkfz.de/record/186736},
}