Bohnenberger, Hanibal

[["dc.bibliographiccitation.firstpage","549"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Cancer Cell"],["dc.bibliographiccitation.lastpage","+"],["dc.bibliographiccitation.volume","31"],["dc.contributor.author","Mohr, Sebastian"],["dc.contributor.author","Döbele, Carmen"],["dc.contributor.author","Comoglio, Federico"],["dc.contributor.author","Berg, Tobias"],["dc.contributor.author","Beck, Julia"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Alexe, Gabriela"],["dc.contributor.author","Corso, Jasmin"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Wachter, Astrid"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Schnuetgen, Frank"],["dc.contributor.author","Cremer, Anjali"],["dc.contributor.author","Haetscher, Nadine"],["dc.contributor.author","Goellner, Stefanie"],["dc.contributor.author","Rouhi, Arefeh"],["dc.contributor.author","Palmqvist, Lars"],["dc.contributor.author","Rieger, Michael A."],["dc.contributor.author","Schroeder, Timm"],["dc.contributor.author","Boenig, Halvard"],["dc.contributor.author","Meuller-Tidow, Carsten"],["dc.contributor.author","Kuchenbauer, Florian"],["dc.contributor.author","Schuetz, Ekkehard"],["dc.contributor.author","Green, Anthony R."],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Stegmaier, Kimberly"],["dc.contributor.author","Humphries, R. Keith"],["dc.contributor.author","Serve, Hubert"],["dc.contributor.author","Oellerich, Thomas"],["dc.date.accessioned","2018-11-07T10:25:02Z"],["dc.date.available","2018-11-07T10:25:02Z"],["dc.date.issued","2017"],["dc.description.abstract","The transcription factor Meis1 drives myeloid leukemogenesis in the context of Hox gene overexpression but is currently considered undruggable. We therefore investigated whether myeloid progenitor cells transformed by Hoxa9 and Meis1 become addicted to targetable signaling pathways. A comprehensive (phospho) proteomic analysis revealed that Meis1 increased Syk protein expression and activity. Syk upregulation occurs through a Meis1-dependent feedback loop. By dissecting this loop, we show that Syk is a direct target of miR-146a, whose expression is indirectly regulated by Meis1 through the transcription factor PU. 1. In the context of Hoxa9 overexpression, Syk signaling induces Meis1, recapitulating several leukemogenic features of Hoxa9/Meis1-driven leukemia. Finally, Syk inhibition disrupts the identified regulatory loop, prolonging survival of mice with Hoxa9/Meis1-driven leukemia."],["dc.identifier.doi","10.1016/j.ccell.2017.03.001"],["dc.identifier.isi","000398670600010"],["dc.identifier.pmid","28399410"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14438"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42772"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Cell Press"],["dc.relation.issn","1878-3686"],["dc.relation.issn","1535-6108"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Hoxa9 and Meis1 Cooperatively Induce Addiction to Syk Signaling by Suppressing miR-146a in Acute Myeloid Leukemia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","19"],["dc.bibliographiccitation.journal","Cancer Research"],["dc.bibliographiccitation.volume","74"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Stroebel, Philipp"],["dc.contributor.author","Henric-Petri, Hannah"],["dc.contributor.author","Lenz, Christof"],["dc.contributor.author","Emmert, Alexander"],["dc.contributor.author","Bremmer, Felix"],["dc.contributor.author","Strecker, Jasmin"],["dc.contributor.author","Holland, Rainer"],["dc.contributor.author","Hinterthaner, Marc"],["dc.contributor.author","Corso, Jasmin"],["dc.contributor.author","Wagner, Sebastian"],["dc.contributor.author","Kueffer, Stefan"],["dc.contributor.author","Sebastian, Martin"],["dc.contributor.author","Bergmann, Lothar"],["dc.contributor.author","Danner, Bernd"],["dc.contributor.author","Schoendube, Friedrich Albert"],["dc.contributor.author","Serve, Hubert"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Oellerich, Thomas"],["dc.date.accessioned","2018-11-07T09:33:49Z"],["dc.date.available","2018-11-07T09:33:49Z"],["dc.date.issued","2014"],["dc.identifier.doi","10.1158/1538-7445.AM2014-2487"],["dc.identifier.isi","000349906903219"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32050"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Cancer Research"],["dc.publisher.place","Philadelphia"],["dc.relation.conference","105th Annual Meeting of the American-Association-for-Cancer-Research (AACR)"],["dc.relation.eventlocation","San Diego, CA"],["dc.relation.issn","1538-7445"],["dc.relation.issn","0008-5472"],["dc.title","Comprehensive quantitative proteomic profiling of lung cancers reveals novel biomarkers and potential drug targets"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","23"],["dc.bibliographiccitation.journal","Blood"],["dc.bibliographiccitation.volume","126"],["dc.contributor.author","Doebele, Carmen"],["dc.contributor.author","Kovar, Johannes"],["dc.contributor.author","Yepes, Diego"],["dc.contributor.author","Muench, Silvia"],["dc.contributor.author","Schnuetgen, Frank"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Koehler, Anne"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Serve, Hubert"],["dc.contributor.author","Oellerich, Thomas"],["dc.date.accessioned","2018-11-07T09:47:45Z"],["dc.date.available","2018-11-07T09:47:45Z"],["dc.date.issued","2015"],["dc.identifier.isi","000368020101291"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35167"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Hematology"],["dc.publisher.place","Washington"],["dc.relation.conference","57th Annual Meeting of the American-Society-of-Hematology"],["dc.relation.eventlocation","Orlando, FL"],["dc.relation.issn","1528-0020"],["dc.relation.issn","0006-4971"],["dc.title","Phosphoproteomic Profiling of the Signaling Output of FLT3-ITD and Its AC220-Resistant Mutants Reveals Profound Signaling Differences and Differential Responsiveness to Inhibition of Downstream Kinases"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","33"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","The Journal of Pathology: Clinical Research"],["dc.bibliographiccitation.lastpage","47"],["dc.bibliographiccitation.volume","8"],["dc.contributor.affiliation","Fichtner, Alexander; 1\r\nInstitute of Pathology\r\nUniversity Medical Centre Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Joost, Jasmin; 1\r\nInstitute of Pathology\r\nUniversity Medical Centre Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Brockmeyer, Philipp; 2\r\nDepartment of Oral and Maxillofacial Surgery\r\nUniversity Medical Centre Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Kauffmann, Philipp; 2\r\nDepartment of Oral and Maxillofacial Surgery\r\nUniversity Medical Centre Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Schliephake, Henning; 2\r\nDepartment of Oral and Maxillofacial Surgery\r\nUniversity Medical Centre Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Hammerstein‐Equord, Alexander; 3\r\nDepartment of Thoracic and Cardiovascular Surgery\r\nUniversity Medical Centre Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Kueffer, Stefan; 1\r\nInstitute of Pathology\r\nUniversity Medical Centre Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Urlaub, Henning; 4\r\nBioanalytical Mass Spectrometry Group\r\nMax Planck Institute for Biophysical Chemistry\r\nGöttingen Germany"],["dc.contributor.affiliation","Oellerich, Thomas; 6\r\nDepartment of Medicine II, Haematology/Oncology\r\nGoethe University\r\nFrankfurt Germany"],["dc.contributor.affiliation","Ströbel, Philipp; 1\r\nInstitute of Pathology\r\nUniversity Medical Centre Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Bohnenberger, Hanibal; 1\r\nInstitute of Pathology\r\nUniversity Medical Centre Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Bremmer, Felix; 1\r\nInstitute of Pathology\r\nUniversity Medical Centre Göttingen\r\nGöttingen Germany"],["dc.contributor.author","Richter, Annika"],["dc.contributor.author","Fichtner, Alexander"],["dc.contributor.author","Joost, Jasmin"],["dc.contributor.author","Brockmeyer, Philipp"],["dc.contributor.author","Kauffmann, Philipp"],["dc.contributor.author","Schliephake, Henning"],["dc.contributor.author","Hammerstein‐Equord, Alexander"],["dc.contributor.author","Kueffer, Stefan"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Oellerich, Thomas"],["dc.contributor.author","Bremmer, Felix"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.date.accessioned","2021-12-01T09:23:20Z"],["dc.date.available","2021-12-01T09:23:20Z"],["dc.date.issued","2021"],["dc.date.updated","2022-03-20T23:05:20Z"],["dc.description.abstract","Abstract The differentiation between a pulmonary metastasis and a newly developed squamous cell carcinoma of the lung in patients with prior head and neck squamous cell carcinoma (HNSCC) is difficult due to a lack of biomarkers but is crucially important for the prognosis and therapy of the affected patient. By using high‐resolution mass spectrometry in combination with stable isotope labelling by amino acids in cell culture, we identified 379 proteins that are differentially expressed in squamous cell carcinomas of the lung and the head and neck. Of those, CAV1, CAV2, LGALS1, LGALS7, CK19, and UGDH were tested by immunohistochemistry on 194 tissue samples (98 lung and 96 HNSCCs). The combination of CAV1 and LGALS7 was able to distinguish the origin of the squamous cell carcinoma with high accuracy (area under the curve 0.876). This biomarker panel was tested on a cohort of 12 clinically classified lung tumours of unknown origin after HNSCC. Nine of those tumours were immunohistochemically classifiable."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2021"],["dc.identifier.doi","10.1002/cjp2.244"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/94624"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-478"],["dc.relation.eissn","2056-4538"],["dc.rights","CC BY-NC-ND 4.0"],["dc.title","Quantitative proteomics identifies biomarkers to distinguish pulmonary from head and neck squamous cell carcinomas by immunohistochemistry"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1550"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","European Journal of Immunology"],["dc.bibliographiccitation.lastpage","1562"],["dc.bibliographiccitation.volume","41"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Oellerich, Thomas"],["dc.contributor.author","Engelke, Michael"],["dc.contributor.author","Hsiao, He-Hsuan"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Wienands, Juergen"],["dc.date.accessioned","2018-11-07T08:55:23Z"],["dc.date.available","2018-11-07T08:55:23Z"],["dc.date.issued","2011"],["dc.description.abstract","Spleen tyrosine kinase Syk provides critical transducer functions for a number of immune cell receptors and has been implicated in the generation of several forms of leukemias. Catalytic activity and the ability of Syk to interact with other signaling elements depend on the phosphorylation status of Syk. We have now identified and quantified the full spectrum of phosphoacceptor sites in human Syk as well as the interactome of Syk in resting and activated B cells by high-resolution mass spectrometry. While the majority of inducible phosphorylations occurred on tyrosine residues, one of the most frequently detected phosphosites encompassed serine 297 located within the linker insert distinguishing the long and short isoforms of Syk. Full-length Syk can associate with more than 25 distinct ligands including the 14-3-3 gamma adaptor protein, which binds directly to phosphoserine 297. The latter complex attenuates inducible plasma membrane recruitment of Syk, thereby limiting antigen receptor-proximal signaling pathways. Collectively, the established ligand library provides a basis to understand the complexity of the Syk signaling network."],["dc.identifier.doi","10.1002/eji.201041326"],["dc.identifier.isi","000291559700007"],["dc.identifier.pmid","21469132"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/22888"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","0014-2980"],["dc.title","Complex phosphorylation dynamics control the composition of the Syk interactome in B cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Oncology Research and Treatment"],["dc.bibliographiccitation.volume","39"],["dc.contributor.author","Walter, Roland"],["dc.contributor.author","Corso, Jasmin"],["dc.contributor.author","Pan, K.-T"],["dc.contributor.author","Doebele, Carmen"],["dc.contributor.author","Yepes, Diego"],["dc.contributor.author","Sellner, L."],["dc.contributor.author","Tomska, Katarzyna"],["dc.contributor.author","Bohnenberger, H."],["dc.contributor.author","Zenz, Thorsten"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Serve, Hubert"],["dc.contributor.author","Oellerich, Thomas"],["dc.date.accessioned","2018-11-07T10:07:37Z"],["dc.date.available","2018-11-07T10:07:37Z"],["dc.date.issued","2016"],["dc.format.extent","219"],["dc.identifier.isi","000385691300540"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/39316"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Karger"],["dc.publisher.place","Basel"],["dc.relation.issn","2296-5262"],["dc.relation.issn","2296-5270"],["dc.title","Elucidation of tonic and activated B cell receptor signaling in Burkitt's lymphoma reveals insights into non-oncogene addiction"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3889"],["dc.bibliographiccitation.issue","19"],["dc.bibliographiccitation.journal","Blood"],["dc.bibliographiccitation.lastpage","3899"],["dc.bibliographiccitation.volume","121"],["dc.contributor.author","Oellerich, Thomas"],["dc.contributor.author","Oellerich, Mark F."],["dc.contributor.author","Engelke, Michael"],["dc.contributor.author","Muench, Silvia"],["dc.contributor.author","Mohr, Sebastian"],["dc.contributor.author","Nimz, Marika"],["dc.contributor.author","Hsiao, He-Hsuan"],["dc.contributor.author","Corso, Jasmin"],["dc.contributor.author","Zhang, J."],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Berg, Tobias"],["dc.contributor.author","Rieger, Michael A."],["dc.contributor.author","Wienands, Juergen"],["dc.contributor.author","Bug, Gesine"],["dc.contributor.author","Brandts, Christian"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Serve, Hubert"],["dc.date.accessioned","2018-11-07T09:24:43Z"],["dc.date.available","2018-11-07T09:24:43Z"],["dc.date.issued","2013"],["dc.description.abstract","Spleen tyrosine kinase (Syk) induces cell survival and proliferation in a high proportion of acute myeloid leukemia (AML) blasts, but the underlying molecular events of Syk signaling have not been investigated. Proteomic techniques have allowed us to identify the multiprotein complex that is nucleated by constitutively active Syk in AML cells. This complex differs from the B-lymphoid Syk interactome with respect to several proteins, especially the integrin receptor Mac-1, the Fc-gamma receptor I (Fc gamma RI), and the transcription factors STAT3 and STAT5. We show in several AML cell line models that tonic signals derived from the Fc-gamma chain lead to Syk-dependent activation of STAT3 and STAT5, which in turn induces cell survival and proliferation. Moreover, stimulation of Mac-1 or Fc gamma RI intensifies the constitutive Syk-mediated STAT3/5 activation in AML cells, a scenario likely to take place in the bone marrow niche. In accordance with these findings, we observed that beta(2) integrins, including Mac-1, trigger proliferation of AML cells in an AML cell/stroma coculture model. Taken together, we identified an oncogenic integrin/Syk/STAT3/5 signaling axis that might serve as a therapeutic target of AML in the future."],["dc.identifier.doi","10.1182/blood-2012-09-457887"],["dc.identifier.isi","000321870900019"],["dc.identifier.pmid","23509157"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29892"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Hematology"],["dc.relation.issn","0006-4971"],["dc.title","beta(2) integrin-derived signals induce cell survival and proliferation of AML blasts by activating a Syk/STAT signaling axis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","19"],["dc.bibliographiccitation.journal","Cancer Research"],["dc.bibliographiccitation.volume","74"],["dc.contributor.author","Oellerich, Thomas"],["dc.contributor.author","Mohr, Sebastian"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Dubey, Anjali"],["dc.contributor.author","Muench, Silvia"],["dc.contributor.author","Wicht, Johannes"],["dc.contributor.author","Oellerich, Mark F."],["dc.contributor.author","Perske, Christina"],["dc.contributor.author","Bug, Gesine"],["dc.contributor.author","Stroebel, Philipp"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Serve, Hubert"],["dc.date.accessioned","2018-11-07T09:33:50Z"],["dc.date.available","2018-11-07T09:33:50Z"],["dc.date.issued","2014"],["dc.identifier.doi","10.1158/1538-7445.AM2014-4203"],["dc.identifier.isi","000349910202180"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32054"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Cancer Research"],["dc.publisher.place","Philadelphia"],["dc.relation.conference","105th Annual Meeting of the American-Association-for-Cancer-Research (AACR)"],["dc.relation.eventlocation","San Diego, CA"],["dc.relation.issn","1538-7445"],["dc.relation.issn","0008-5472"],["dc.title","A transducer module consisting of Toll-like receptor 9 and Bruton's tyrosine kinase triggers acute myeloid leukemia blast proliferation"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1700"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Leukemia"],["dc.bibliographiccitation.lastpage","1712"],["dc.bibliographiccitation.volume","33"],["dc.contributor.author","Hoang, Van T."],["dc.contributor.author","Verma, Divij"],["dc.contributor.author","Godavarthy, Parimala Sonika"],["dc.contributor.author","Llavona, Pablo"],["dc.contributor.author","Steiner, Marlene"],["dc.contributor.author","Gerlach, Katharina"],["dc.contributor.author","Michels, Birgitta E."],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Wachter, Astrid"],["dc.contributor.author","Oellerich, Thomas"],["dc.contributor.author","Müller-Kuller, Uta"],["dc.contributor.author","Weissenberger, Eva"],["dc.contributor.author","Voutsinas, Jenna M."],["dc.contributor.author","Oehler, Vivian G."],["dc.contributor.author","Farin, Henner F."],["dc.contributor.author","Zörnig, Martin"],["dc.contributor.author","Krause, Daniela S."],["dc.date.accessioned","2020-12-10T18:09:34Z"],["dc.date.available","2020-12-10T18:09:34Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1038/s41375-018-0358-8"],["dc.identifier.eissn","1476-5551"],["dc.identifier.issn","0887-6924"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/73695"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","The transcriptional regulator FUBP1 influences disease outcome in murine and human myeloid leukemia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","250"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Nature Medicine"],["dc.bibliographiccitation.lastpage","255"],["dc.bibliographiccitation.volume","23"],["dc.contributor.author","Schneider, Constanze"],["dc.contributor.author","Oellerich, Thomas"],["dc.contributor.author","Baldauf, Hanna-Mari"],["dc.contributor.author","Schwarz, Sarah-Marie"],["dc.contributor.author","Thomas, Dominique"],["dc.contributor.author","Flick, Robert"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Kaderali, Lars"],["dc.contributor.author","Stegmann, Lena"],["dc.contributor.author","Cremer, Anjali"],["dc.contributor.author","Martin, Margarethe"],["dc.contributor.author","Lohmeyer, Julian"],["dc.contributor.author","Michaelis, Martin"],["dc.contributor.author","Hornung, Veit"],["dc.contributor.author","Schliemann, Christoph"],["dc.contributor.author","Berdel, Wolfgang E."],["dc.contributor.author","Hartmann, Wolfgang"],["dc.contributor.author","Wardelmann, Eva"],["dc.contributor.author","Comoglio, Federico"],["dc.contributor.author","Hansmann, Martin-Leo"],["dc.contributor.author","Yakunin, Alexander F."],["dc.contributor.author","Geisslinger, Gerd"],["dc.contributor.author","Stroebel, Philipp"],["dc.contributor.author","Ferreiros, Nerea"],["dc.contributor.author","Serve, Hubert"],["dc.contributor.author","Keppler, Oliver T."],["dc.contributor.author","Cinatl, Jindrich, Jr."],["dc.date.accessioned","2018-11-07T10:28:09Z"],["dc.date.available","2018-11-07T10:28:09Z"],["dc.date.issued","2017"],["dc.description.abstract","The nucleoside analog cytarabine (Ara-C) is an essential component of primary and salvage chemotherapy regimens for acute myeloid leukemia (AML). After cellular uptake, Ara-C is converted into its therapeutically active triphosphate metabolite, Ara-CTP, which exerts antileukemic effects, primarily by inhibiting DNA synthesis in proliferating cells'. Currently, a substantial fraction of patients with AML fail to respond effectively to Ara-C therapy, and reliable biomarkers for predicting the therapeutic response to Ara-C are lacking(2,3). SAMHD1 is a deoxynucleoside triphosphate (dNTP) triphosphohydrolase that cleaves physiological dNTPs into deoxyribonucleosides and inorganic triphosphate(4,5). Although it has been postulated that SAMHD1 sensitizes cancer cells to nucleoside-analog derivatives through the depletion of competing dNTPs6, we show here that SAMHD1 reduces Ara-C cytotoxicity in AML cells. Mechanistically, dGTP-activated SAMHD1 hydrolyzes Ara-CTP, which results in a drastic reduction of Ara-CTP in leukemic cells. Loss of SAMHD1 activity through genetic depletion, mutational inactivation of its triphosphohydrolase activity or proteasomal degradation using specialized, virus-like particles(7,8) potentiates the cytotoxicity of Ara-C in AML cells. In mouse models of retroviral AML transplantation, as well as in retrospective analyses of adult patients with AML, the response to Ara-C-containing therapy was inversely correlated with SAMHD1 expression. These results identify SAMHD1 as a potential biomarker for the stratification of patients with AML who might best respond to Ara-C-based therapy and as a target for treating Ara-C-refractory AML."],["dc.identifier.doi","10.1038/nm.4255"],["dc.identifier.isi","000393729000017"],["dc.identifier.pmid","27991919"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43359"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1546-170X"],["dc.relation.issn","1078-8956"],["dc.title","SAMHD1 is a biomarker for cytarabine response and a therapeutic target in acute myeloid leukemia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]