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dc.contributor.authorTakaomi, Sanda
dc.contributor.authorTyner, Jeffrey W.
dc.contributor.authorGutierrez, Alejandro
dc.contributor.authorNgo, Vu N.
dc.contributor.authorGlover, Jason
dc.contributor.authorChang, Bill H.
dc.contributor.authorYost, Arla
dc.contributor.authorMa, Wenxue
dc.contributor.authorFleischman, Angela G.
dc.contributor.authorZhou, Wenjun
dc.contributor.authorYang, Yandan
dc.contributor.authorKleppe, Maria
dc.contributor.authorAhn, Yebin
dc.contributor.authorTatarek, Jessica
dc.contributor.authorKelliher, Michelle A.
dc.contributor.authorNeuberg, Donna S.
dc.contributor.authorLevine, Ross L.
dc.contributor.authorMoriggl, Richard
dc.contributor.authorMuller, Mathias
dc.contributor.authorGray, Nathanael S.
dc.contributor.authorJamieson, Catriona H. M.
dc.contributor.authorWeng, Andrew P.
dc.contributor.authorStaudt, Louis M.
dc.contributor.authorDruker, Brian J.
dc.contributor.authorLook, A. Thomas
dc.date2022-08-11T08:08:30.000
dc.date.accessioned2022-08-23T15:57:16Z
dc.date.available2022-08-23T15:57:16Z
dc.date.issued2013-05-01
dc.date.submitted2013-06-18
dc.identifier.citationCancer Discov. 2013 May;3(5):564-577. Epub 2013 Mar 7. <a href="http://dx.doi.org/10.1158/2159-8290.CD-12-0504">Link to article on publisher's site</a>
dc.identifier.issn2159-8274 (Linking)
dc.identifier.doi10.1158/2159-8290.CD-12-0504
dc.identifier.pmid23471820
dc.identifier.urihttp://hdl.handle.net/20.500.14038/30158
dc.description.abstractTargeted molecular therapy has yielded remarkable outcomes in certain cancers, but specific therapeutic targets remain elusive for many others. As a result of two independent RNA interference (RNAi) screens, we identified pathway dependence on a member of the Janus-activated kinase (JAK) tyrosine kinase family, TYK2, and its downstream effector STAT1, in T-cell acute lymphoblastic leukemia (T-ALL). Gene knockdown experiments consistently showed TYK2 dependence in both T-ALL primary specimens and cell lines, and a small-molecule inhibitor of JAK activity induced T-ALL cell death. Activation of this TYK2-STAT1 pathway in T-ALL cell lines occurs by gain-of-function TYK2 mutations or activation of interleukin (IL)-10 receptor signaling, and this pathway mediates T-ALL cell survival through upregulation of the antiapoptotic protein BCL2. These findings indicate that in many T-ALL cases, the leukemic cells are dependent upon the TYK2-STAT1-BCL2 pathway for continued survival, supporting the development of molecular therapies targeting TYK2 and other components of this pathway.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=23471820&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1158/2159-8290.CD-12-0504
dc.subjectLeukemia, Biphenotypic, Acute
dc.subjectTYK2 Kinase
dc.subjectSTAT1 Transcription Factor
dc.subjectProto-Oncogene Proteins c-bcl-2
dc.subjectCancer Biology
dc.subjectNeoplasms
dc.subjectOncology
dc.titleTYK2-STAT1-BCL2 Pathway Dependence in T-cell Acute Lymphoblastic Leukemia
dc.typeJournal Article
dc.source.journaltitleCancer discovery
dc.source.volume3
dc.source.issue5
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/40
dc.identifier.contextkey4236671
html.description.abstract<p>Targeted molecular therapy has yielded remarkable outcomes in certain cancers, but specific therapeutic targets remain elusive for many others. As a result of two independent RNA interference (RNAi) screens, we identified pathway dependence on a member of the Janus-activated kinase (JAK) tyrosine kinase family, TYK2, and its downstream effector STAT1, in T-cell acute lymphoblastic leukemia (T-ALL). Gene knockdown experiments consistently showed TYK2 dependence in both T-ALL primary specimens and cell lines, and a small-molecule inhibitor of JAK activity induced T-ALL cell death. Activation of this TYK2-STAT1 pathway in T-ALL cell lines occurs by gain-of-function TYK2 mutations or activation of interleukin (IL)-10 receptor signaling, and this pathway mediates T-ALL cell survival through upregulation of the antiapoptotic protein BCL2. These findings indicate that in many T-ALL cases, the leukemic cells are dependent upon the TYK2-STAT1-BCL2 pathway for continued survival, supporting the development of molecular therapies targeting TYK2 and other components of this pathway.</p>
dc.identifier.submissionpathfaculty_pubs/40
dc.contributor.departmentDepartment of Cancer Biology
dc.source.pages564-577


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