| First Author | Hoelbl A | Year | 2010 |
| Journal | EMBO Mol Med | Volume | 2 |
| Issue | 3 | Pages | 98-110 |
| PubMed ID | 20201032 | Mgi Jnum | J:267888 |
| Mgi Id | MGI:6270245 | Doi | 10.1002/emmm.201000062 |
| Citation | Hoelbl A, et al. (2010) Stat5 is indispensable for the maintenance of bcr/abl-positive leukaemia. EMBO Mol Med 2(3):98-110 |
| abstractText | 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). |
