000142742 001__ 142742
000142742 005__ 20240229105151.0
000142742 0247_ $$2doi$$a10.1038/leu.2017.252
000142742 0247_ $$2pmid$$apmid:28804127
000142742 0247_ $$2ISSN$$a0887-6924
000142742 0247_ $$2ISSN$$a1476-5551
000142742 0247_ $$2altmetric$$aaltmetric:23915761
000142742 037__ $$aDKFZ-2019-00459
000142742 041__ $$aeng
000142742 082__ $$a610
000142742 1001_ $$aAndersson, E. I.$$b0
000142742 245__ $$aDiscovery of novel drug sensitivities in T-PLL by high-throughput ex vivo drug testing and mutation profiling.
000142742 260__ $$aLondon$$bSpringer Nature$$c2018
000142742 3367_ $$2DRIVER$$aarticle
000142742 3367_ $$2DataCite$$aOutput Types/Journal article
000142742 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1661339942_30652
000142742 3367_ $$2BibTeX$$aARTICLE
000142742 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000142742 3367_ $$00$$2EndNote$$aJournal Article
000142742 520__ $$aT-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive neoplasm of mature T-cells with an urgent need for rationally designed therapies to address its notoriously chemo-refractory behavior. The median survival of T-PLL patients is <2 years and clinical trials are difficult to execute. Here we systematically explored the diversity of drug responses in T-PLL patient samples using an ex vivo drug sensitivity and resistance testing platform and correlated the findings with somatic mutations and gene expression profiles. Intriguingly, all T-PLL samples were sensitive to the cyclin-dependent kinase inhibitor SNS-032, which overcame stromal-cell-mediated protection and elicited robust p53-activation and apoptosis. Across all patients, the most effective classes of compounds were histone deacetylase, phosphoinositide-3 kinase/AKT/mammalian target of rapamycin, heat-shock protein 90 and BH3-family protein inhibitors as well as p53 activators, indicating previously unexplored, novel targeted approaches for treating T-PLL. Although Janus-activated kinase-signal transducer and activator of transcription factor (JAK-STAT) pathway mutations were common in T-PLL (71% of patients), JAK-STAT inhibitor responses were not directly linked to those or other T-PLL-specific lesions. Overall, we found that genetic markers do not readily translate into novel effective therapeutic vulnerabilities. In conclusion, novel classes of compounds with high efficacy in T-PLL were discovered with the comprehensive ex vivo drug screening platform warranting further studies of synergisms and clinical testing.
000142742 536__ $$0G:(DE-HGF)POF3-317$$a317 - Translational cancer research (POF3-317)$$cPOF3-317$$fPOF III$$x0
000142742 588__ $$aDataset connected to CrossRef, PubMed,
000142742 650_7 $$2NLM Chemicals$$aAntineoplastic Agents
000142742 650_7 $$2NLM Chemicals$$aBiomarkers, Tumor
000142742 650_7 $$2NLM Chemicals$$aN-(5-(((5-(1,1-dimethylethyl)-2-oxazolyl)methyl)thio)-2-thiazolyl)-4-piperidinecarboxamide
000142742 650_7 $$2NLM Chemicals$$aOxazoles
000142742 650_7 $$2NLM Chemicals$$aProtein Kinase Inhibitors
000142742 650_7 $$2NLM Chemicals$$aSTAT Transcription Factors
000142742 650_7 $$2NLM Chemicals$$aThiazoles
000142742 650_7 $$0EC 2.7.10.2$$2NLM Chemicals$$aJanus Kinases
000142742 7001_ $$aPützer, S.$$b1
000142742 7001_ $$aYadav, B.$$b2
000142742 7001_ $$aDufva, O.$$b3
000142742 7001_ $$aKhan, S.$$b4
000142742 7001_ $$aHe, L.$$b5
000142742 7001_ $$0P:(DE-He78)b07a76205b49e86733668b7201520d19$$aSellner, Leopold$$b6$$udkfz
000142742 7001_ $$aSchrader, A.$$b7
000142742 7001_ $$aCrispatzu, G.$$b8
000142742 7001_ $$aOleś, M.$$b9
000142742 7001_ $$aZhang, H.$$b10
000142742 7001_ $$aAdnan-Awad, S.$$b11
000142742 7001_ $$aLagström, S.$$b12
000142742 7001_ $$aBellanger, D.$$b13
000142742 7001_ $$aMpindi, J. P.$$b14
000142742 7001_ $$00000-0001-5056-4750$$aEldfors, S.$$b15
000142742 7001_ $$aPemovska, T.$$b16
000142742 7001_ $$aPietarinen, P.$$b17
000142742 7001_ $$aLauhio, A.$$b18
000142742 7001_ $$0P:(DE-He78)b19e65a29d89d299cf5a04670a7ff0ae$$aTomska, K.$$b19$$udkfz
000142742 7001_ $$aCuesta-Mateos, C.$$b20
000142742 7001_ $$aFaber, E.$$b21
000142742 7001_ $$aKoschmieder, S.$$b22
000142742 7001_ $$aBrümmendorf, T. H.$$b23
000142742 7001_ $$aKytölä, S.$$b24
000142742 7001_ $$aSavolainen, E-R$$b25
000142742 7001_ $$aSiitonen, T.$$b26
000142742 7001_ $$aEllonen, P.$$b27
000142742 7001_ $$00000-0002-3231-0332$$aKallioniemi, O.$$b28
000142742 7001_ $$aWennerberg, K.$$b29
000142742 7001_ $$aDing, W.$$b30
000142742 7001_ $$aStern, M-H$$b31
000142742 7001_ $$00000-0002-0474-2218$$aHuber, W.$$b32
000142742 7001_ $$00000-0002-3986-9892$$aAnders, S.$$b33
000142742 7001_ $$aTang, J.$$b34
000142742 7001_ $$aAittokallio, T.$$b35
000142742 7001_ $$0P:(DE-He78)f3d5f16b49eb47520def635be98d5576$$aZenz, T.$$b36$$udkfz
000142742 7001_ $$aHerling, M.$$b37
000142742 7001_ $$aMustjoki, S.$$b38
000142742 773__ $$0PERI:(DE-600)2008023-2$$a10.1038/leu.2017.252$$gVol. 32, no. 3, p. 774 - 787$$n3$$p774 - 787$$tLeukemia$$v32$$x1476-5551$$y2018
000142742 909CO $$ooai:inrepo02.dkfz.de:142742$$pVDB
000142742 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)b07a76205b49e86733668b7201520d19$$aDeutsches Krebsforschungszentrum$$b6$$kDKFZ
000142742 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)b19e65a29d89d299cf5a04670a7ff0ae$$aDeutsches Krebsforschungszentrum$$b19$$kDKFZ
000142742 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)f3d5f16b49eb47520def635be98d5576$$aDeutsches Krebsforschungszentrum$$b36$$kDKFZ
000142742 9131_ $$0G:(DE-HGF)POF3-317$$1G:(DE-HGF)POF3-310$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vTranslational cancer research$$x0
000142742 9141_ $$y2018
000142742 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000142742 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000142742 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bLEUKEMIA : 2017
000142742 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000142742 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search
000142742 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC
000142742 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List
000142742 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index
000142742 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000142742 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000142742 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences
000142742 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews
000142742 915__ $$0StatID:(DE-HGF)9910$$2StatID$$aIF >= 10$$bLEUKEMIA : 2017
000142742 9201_ $$0I:(DE-He78)G100-20160331$$kG100$$lTranslationale Onkologie$$x0
000142742 9201_ $$0I:(DE-He78)G250-20160331$$kG250$$lMolekulare Therapie in der Hämatologie und Onkologie$$x1
000142742 980__ $$ajournal
000142742 980__ $$aVDB
000142742 980__ $$aI:(DE-He78)G100-20160331
000142742 980__ $$aI:(DE-He78)G250-20160331
000142742 980__ $$aUNRESTRICTED