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dc.contributor.authorLiang, Huan-Chang
dc.contributor.authorCostanza, Mariantonia
dc.contributor.authorPrutsch, Nicole
dc.contributor.authorZimmerman, Mark W
dc.contributor.authorGurnhofer, Elisabeth
dc.contributor.authorMontes-Mojarro, Ivonne A
dc.contributor.authorAbraham, Brian J
dc.contributor.authorProkoph, Nina
dc.contributor.authorStoiber, Stefan
dc.contributor.authorTangermann, Simone
dc.contributor.authorLobello, Cosimo
dc.contributor.authorOppelt, Jan
dc.contributor.authorAnagnostopoulos, Ioannis
dc.contributor.authorHielscher, Thomas
dc.contributor.authorPervez, Shahid
dc.contributor.authorKlapper, Wolfram
dc.contributor.authorZammarchi, Francesca
dc.contributor.authorSilva, Daniel-Adriano
dc.contributor.authorGarcia, K Christopher
dc.contributor.authorBaker, David
dc.contributor.authorJanz, Martin
dc.contributor.authorSchleussner, Nikolai
dc.contributor.authorFend, Falko
dc.contributor.authorPospíšilová, Šárka
dc.contributor.authorJaniková, Andrea
dc.contributor.authorWallwitz, Jacqueline
dc.contributor.authorStoiber, Dagmar
dc.contributor.authorSimonitsch-Klupp, Ingrid
dc.contributor.authorCerroni, Lorenzo
dc.contributor.authorPileri, Stefano
dc.contributor.authorde Leval, Laurence
dc.contributor.authorSibon, David
dc.contributor.authorFataccioli, Virginie
dc.contributor.authorGaulard, Philippe
dc.contributor.authorAssaf, Chalid
dc.contributor.authorKnörr, Fabian
dc.contributor.authorDamm-Welk, Christine
dc.contributor.authorWoessmann, Wilhelm
dc.contributor.authorTurner, Suzanne D
dc.contributor.authorLook, A Thomas
dc.contributor.authorMathas, Stephan
dc.contributor.authorKenner, Lukas
dc.contributor.authorMerkel, Olaf
dc.date.accessioned2021-10-25T00:39:23Z
dc.date.available2021-10-25T00:39:23Z
dc.date.issued2021-09-22
dc.identifier.issn2041-1723
dc.identifier.otherPMC8458384
dc.identifier.other34552066
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/329836
dc.description.abstractAnaplastic large cell lymphoma (ALCL), an aggressive CD30-positive T-cell lymphoma, comprises systemic anaplastic lymphoma kinase (ALK)-positive, and ALK-negative, primary cutaneous and breast implant-associated ALCL. Prognosis of some ALCL subgroups is still unsatisfactory, and already in second line effective treatment options are lacking. To identify genes defining ALCL cell state and dependencies, we here characterize super-enhancer regions by genome-wide H3K27ac ChIP-seq. In addition to known ALCL key regulators, the AP-1-member BATF3 and IL-2 receptor (IL2R)-components are among the top hits. Specific and high-level IL2R expression in ALCL correlates with BATF3 expression. Confirming a regulatory link, IL-2R-expression decreases following BATF3 knockout, and BATF3 is recruited to IL2R regulatory regions. Functionally, IL-2, IL-15 and Neo-2/15, a hyper-stable IL-2/IL-15 mimic, accelerate ALCL growth and activate STAT1, STAT5 and ERK1/2. In line, strong IL-2Rα-expression in ALCL patients is linked to more aggressive clinical presentation. Finally, an IL-2Rα-targeting antibody-drug conjugate efficiently kills ALCL cells in vitro and in vivo. Our results highlight the importance of the BATF3/IL-2R-module for ALCL biology and identify IL-2Rα-targeting as a promising treatment strategy for ALCL.
dc.languageeng
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 2041-1723
dc.sourcenlmid: 101528555
dc.titleSuper-enhancer-based identification of a BATF3/IL-2R-module reveals vulnerabilities in anaplastic large cell lymphoma.
dc.typeArticle
dc.date.updated2021-10-25T00:39:22Z
prism.issueIdentifier1
prism.publicationNameNature communications
prism.volume12
dc.identifier.doi10.17863/CAM.77281
rioxxterms.versionofrecord10.1038/s41467-021-25379-9
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidLiang, Huan-Chang [0000-0003-2612-3714]
dc.contributor.orcidCostanza, Mariantonia [0000-0002-8959-1083]
dc.contributor.orcidZimmerman, Mark W [0000-0003-2489-3889]
dc.contributor.orcidMontes-Mojarro, Ivonne A [0000-0003-0636-7623]
dc.contributor.orcidAbraham, Brian J [0000-0001-8085-3027]
dc.contributor.orcidProkoph, Nina [0000-0002-6429-9895]
dc.contributor.orcidStoiber, Stefan [0000-0003-3293-867X]
dc.contributor.orcidOppelt, Jan [0000-0002-3076-4840]
dc.contributor.orcidKlapper, Wolfram [0000-0001-7208-4117]
dc.contributor.orcidSilva, Daniel-Adriano [0000-0002-3195-9009]
dc.contributor.orcidGarcia, K Christopher [0000-0001-9273-0278]
dc.contributor.orcidBaker, David [0000-0001-7896-6217]
dc.contributor.orcidJanz, Martin [0000-0002-1127-0044]
dc.contributor.orcidFend, Falko [0000-0002-5496-293X]
dc.contributor.orcidde Leval, Laurence [0000-0003-3994-516X]
dc.contributor.orcidTurner, Suzanne D [0000-0002-8439-4507]
dc.contributor.orcidLook, A Thomas [0000-0001-7851-8617]
dc.contributor.orcidMathas, Stephan [0000-0001-9626-1413]
dc.contributor.orcidKenner, Lukas [0000-0003-2184-1338]
dc.contributor.orcidMerkel, Olaf [0000-0001-5089-344X]
pubs.funder-project-idEC | Horizon 2020 Framework Programme (675712)
pubs.funder-project-idAustrian Science Fund FWF (P 26011, P32579, P 29251)


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International