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000145055 0247_ $$2doi$$a10.1038/s41375-019-0618-2
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000145055 0247_ $$2ISSN$$a0887-6924
000145055 0247_ $$2ISSN$$a1476-5551
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000145055 037__ $$aDZNE-2020-00415
000145055 041__ $$aEnglish
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000145055 1001_ $$0P:(DE-HGF)0$$aRiabinska, Arina$$b0$$eCorresponding author
000145055 245__ $$aATM activity in T cells is critical for immune surveillance of lymphoma in vivo.
000145055 260__ $$aLondon$$bSpringer Nature$$c2020
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000145055 264_1 $$2Crossref$$3print$$bSpringer Science and Business Media LLC$$c2020-03-01
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000145055 520__ $$aThe proximal DNA damage response kinase ATM is frequently inactivated in human malignancies. Germline mutations in the ATM gene cause Ataxia-telangiectasia (A-T), characterized by cerebellar ataxia and cancer predisposition. Whether ATM deficiency impacts on tumor initiation or also on the maintenance of the malignant state is unclear. Here, we show that Atm reactivation in initially Atm-deficient B- and T cell lymphomas induces tumor regression. We further find a reduced T cell abundance in B cell lymphomas from Atm-defective mice and A-T patients. Using T cell-specific Atm-knockout models, as well as allogeneic transplantation experiments, we pinpoint impaired immune surveillance as a contributor to cancer predisposition and development. Moreover, we demonstrate that Atm-deficient T cells display impaired proliferation capacity upon stimulation, due to replication stress. Altogether, our data indicate that T cell-specific restoration of ATM activity or allogeneic hematopoietic stem cell transplantation may prevent lymphomagenesis in A-T patients.
000145055 536__ $$0G:(DE-HGF)POF3-342$$a342 - Disease Mechanisms and Model Systems (POF3-342)$$cPOF3-342$$fPOF III$$x0
000145055 542__ $$2Crossref$$i2019-11-05$$uhttp://www.springer.com/tdm
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000145055 650_2 $$2MeSH$$aAlleles
000145055 650_2 $$2MeSH$$aAnimals
000145055 650_2 $$2MeSH$$aAtaxia Telangiectasia Mutated Proteins: metabolism
000145055 650_2 $$2MeSH$$aCell Proliferation
000145055 650_2 $$2MeSH$$aEtoposide: pharmacology
000145055 650_2 $$2MeSH$$aHematopoietic Stem Cell Transplantation
000145055 650_2 $$2MeSH$$aLymphoma: immunology
000145055 650_2 $$2MeSH$$aLymphoma: metabolism
000145055 650_2 $$2MeSH$$aMice
000145055 650_2 $$2MeSH$$aMice, Knockout
000145055 650_2 $$2MeSH$$aT-Lymphocytes: immunology
000145055 650_2 $$2MeSH$$aT-Lymphocytes: metabolism
000145055 650_2 $$2MeSH$$aTransplantation, Homologous
000145055 650_2 $$2MeSH$$aTreatment Outcome
000145055 7001_ $$aLehrmann, Daria$$b1
000145055 7001_ $$aJachimowicz, Ron Daniel$$b2
000145055 7001_ $$aKnittel, Gero$$b3
000145055 7001_ $$0P:(DE-HGF)0$$aFritz, Christian$$b4
000145055 7001_ $$aSchmitt, Anna$$b5
000145055 7001_ $$aGeyer, Aenne$$b6
000145055 7001_ $$aHeneweer, Carola$$b7
000145055 7001_ $$aWittersheim, Maike$$b8
000145055 7001_ $$aFrenzel, Lukas P$$b9
000145055 7001_ $$aTorgovnick, Alessandro$$b10
000145055 7001_ $$aWiederstein, Janica Lea$$b11
000145055 7001_ $$aWunderlich, Claudia Maria$$b12
000145055 7001_ $$aOrtmann, Monika$$b13
000145055 7001_ $$aPaillard, Arlette$$b14
000145055 7001_ $$aWößmann, Wilhelm$$b15
000145055 7001_ $$aBorkhardt, Arndt$$b16
000145055 7001_ $$aBurdach, Stefan$$b17
000145055 7001_ $$aHansmann, Martin-Leo$$b18
000145055 7001_ $$aRosenwald, Andreas$$b19
000145055 7001_ $$aPerner, Sven$$b20
000145055 7001_ $$aMall, Gita$$b21
000145055 7001_ $$0P:(DE-HGF)0$$aKlapper, Wolfram$$b22
000145055 7001_ $$0P:(DE-2719)2811002$$aMerseburg, Andrea$$b23$$udzne
000145055 7001_ $$aKrüger, Marcus$$b24
000145055 7001_ $$aGrüll, Holger$$b25
000145055 7001_ $$aPersigehl, Thorsten$$b26
000145055 7001_ $$0P:(DE-HGF)0$$aWunderlich, Frank Thomas$$b27
000145055 7001_ $$aPeifer, Martin$$b28
000145055 7001_ $$aUtermöhlen, Olaf$$b29
000145055 7001_ $$aBüttner, Reinhard$$b30
000145055 7001_ $$aBeleggia, Filippo$$b31
000145055 7001_ $$aReinhardt, Hans Christian$$b32
000145055 77318 $$2Crossref$$3journal-article$$a10.1038/s41375-019-0618-2$$b : Springer Science and Business Media LLC, 2019-11-05$$n3$$p771-786$$tLeukemia$$v34$$x0887-6924$$y2019
000145055 773__ $$0PERI:(DE-600)2008023-2$$a10.1038/s41375-019-0618-2$$gVol. 34, no. 3, p. 771 - 786$$n3$$p771-786$$tLeukemia$$v34$$x0887-6924$$y2020
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