Open AccessStat5 is indispensable for the maintenance of bcr/abl ‐positive leukaemia
Author(s) -
Hoelbl Andrea,
Schuster Christian,
Kovacic Boris,
Zhu Bingmei,
Wickre Mark,
Hoelzl Maria A.,
Fajmann Sabine,
Grebien Florian,
Warsch Wolfgang,
Stengl Gabriele,
Hennighausen Lothar,
Poli Valeria,
Beug Hartmut,
Moriggl Richard,
Sexl Veronika
Publication year - 2010
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.1002/emmm.201000062
Subject(s) - stat5 , cancer research , breakpoint cluster region , imatinib , biology , oncogene , stat3 , myeloid leukemia , cancer , signal transduction , cell cycle , microbiology and biotechnology , receptor , genetics
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).