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Publikationstyp: Zeitschriftenaufsatz
Dokumenttyp: Originalarbeit

Jahr: 2010

AutorInnen: Hoelbl, A; Schuster, C; Kovacic, B; Zhu, B; Wickre, M; Hoelzl, MA; Fajmann, S; Grebien, F; Warsch, W; Stengl, G; Hennighausen, L; Poli, V; Beug, H; Moriggl, R; Sexl, V

Titel: Stat5 is indispensable for the maintenance of bcr/abl-positive leukaemia.

Quelle: EMBO Mol Med. 2010; 2(3):98-110

Autor/innen der Vetmeduni Vienna:

Grebien Florian
Hölbl-Kovacic Andrea
Sexl Veronika

Diese Publikation wurde nicht im Namen der Vetmeduni Vienna erstellt und ist deshalb ausschließlich der persönlichen Publikationsliste des/der Autors/Autorin zugeordnet!

Zugehörige(s) Projekt(e): Flow cytometric signal typing for therapy response

Tumourigenesis caused by the Bcr/Abl oncoprotein is a multi-step process proceeding from initial to tumour-maintaining events and finally results in a complex tumour-supporting network. A key to successful cancer therapy is the identification of critical functional nodes in an oncogenic network required for disease maintenance. So far, the transcription factors Stat3 and Stat5a/b have been implicated in bcr/abl-induced initial transformation. However, to qualify as a potential drug target, a signalling pathway must be required for the maintenance of the leukaemic state. Data on the roles of Stat3 or Stat5a/b in leukaemia maintenance are elusive. Here, we show that both, Stat3 and Stat5 are necessary for initial transformation. However, Stat5- but not Stat3-deletion induces G(0)/G(1) cell cycle arrest and apoptosis of imatinib-sensitive and imatinib-resistant stable leukaemic cells in vitro. Accordingly, Stat5-abrogation led to effective elimination of myeloid and lymphoid leukaemia maintenance in vivo. Hence, we identified Stat5 as a vulnerable point in the oncogenic network downstream of Bcr/Abl representing a case of non-oncogene addiction (NOA).

Keywords Pubmed: Animals
Cell Cycle
Gene Deletion
Genes, abl
Mice, Inbred C57BL
Mice, Knockout
Proto-Oncogene Proteins c-bcr/genetics
STAT3 Transcription Factor/genetics
STAT3 Transcription Factor/metabolism*
STAT5 Transcription Factor/genetics
STAT5 Transcription Factor/metabolism*

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