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EMBO Mol Med. 2010 Mar;2(3):98-110. doi: 10.1002/emmm.201000062.

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

Author information

1
Institute of Pharmacology, Centre of Biomolecular Medicine and Pharmacology, Medical University of Vienna, Austria.

Abstract

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).

PMID:
20201032
PMCID:
PMC2906698
DOI:
10.1002/emmm.201000062
[Indexed for MEDLINE]
Free PMC Article

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