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@ARTICLE{Riabinska:145055,
author = {Riabinska, Arina and Lehrmann, Daria and Jachimowicz, Ron
Daniel and Knittel, Gero and Fritz, Christian and Schmitt,
Anna and Geyer, Aenne and Heneweer, Carola and Wittersheim,
Maike and Frenzel, Lukas P and Torgovnick, Alessandro and
Wiederstein, Janica Lea and Wunderlich, Claudia Maria and
Ortmann, Monika and Paillard, Arlette and Wößmann, Wilhelm
and Borkhardt, Arndt and Burdach, Stefan and Hansmann,
Martin-Leo and Rosenwald, Andreas and Perner, Sven and Mall,
Gita and Klapper, Wolfram and Merseburg, Andrea and Krüger,
Marcus and Grüll, Holger and Persigehl, Thorsten and
Wunderlich, Frank Thomas and Peifer, Martin and Utermöhlen,
Olaf and Büttner, Reinhard and Beleggia, Filippo and
Reinhardt, Hans Christian},
title = {{ATM} activity in {T} cells is critical for immune
surveillance of lymphoma in vivo.},
journal = {Leukemia},
volume = {34},
number = {3},
issn = {0887-6924},
address = {London},
publisher = {Springer Nature},
reportid = {DZNE-2020-00415},
pages = {771-786},
year = {2020},
abstract = {The proximal DNA damage response kinase ATM is frequently
inactivated in human malignancies. Germline mutations in the
ATM gene cause Ataxia-telangiectasia (A-T), characterized by
cerebellar ataxia and cancer predisposition. Whether ATM
deficiency impacts on tumor initiation or also on the
maintenance of the malignant state is unclear. Here, we show
that Atm reactivation in initially Atm-deficient B- and T
cell lymphomas induces tumor regression. We further find a
reduced T cell abundance in B cell lymphomas from
Atm-defective mice and A-T patients. Using T cell-specific
Atm-knockout models, as well as allogeneic transplantation
experiments, we pinpoint impaired immune surveillance as a
contributor to cancer predisposition and development.
Moreover, we demonstrate that Atm-deficient T cells display
impaired proliferation capacity upon stimulation, due to
replication stress. Altogether, our data indicate that T
cell-specific restoration of ATM activity or allogeneic
hematopoietic stem cell transplantation may prevent
lymphomagenesis in A-T patients.},
keywords = {Alleles / Animals / Ataxia Telangiectasia Mutated Proteins:
metabolism / Cell Proliferation / Etoposide: pharmacology /
Hematopoietic Stem Cell Transplantation / Lymphoma:
immunology / Lymphoma: metabolism / Mice / Mice, Knockout /
T-Lymphocytes: immunology / T-Lymphocytes: metabolism /
Transplantation, Homologous / Treatment Outcome},
cin = {AG Isbrandt},
ddc = {610},
cid = {I:(DE-2719)1011003},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:31690822},
doi = {10.1038/s41375-019-0618-2},
url = {https://pub.dzne.de/record/145055},
}