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Recently, BCR\/ABL has been shown to activate survivin, an important regulator of cell growth and survival, but the precise molecular mechanisms behind its expression and consequences thereof in CML cells remain unclear. Here, we reported that BCR\/ABL promotes survivin expression and its cytoplasmic accumulation. The increase of survivin was largely controlled at the transcriptional level through a mechanism mediated by JAK2\/PI3K signal pathways that activated c\u2010Myc, leading to transactivation of survivin promoter. Dynamic down\u2010regulation of survivin was a key event involved in imatinib\u2010induced cell death while forced expression of survivin partially counteracted imatinib's effect on cell survival. Additionally, shRNA\u2010mediated silencing of survivin or c\u2010Myc eradicated colony formation of K562 cells in semi\u2010solid culture system, implying an essential role for this transcriptional network in BCR\/ABL\u2010mediated cell transformation and survival. Finally, interruption of c\u2010Myc activity by 10058\u2010F4 exerted an anti\u2010leukaemia effect with a synergistic interaction with imatinib and overcame the anti\u2010apoptosis rescued by IL\u20103 supplement. In conclusion, we have identified JAK2\/PI3K\u2010mediated and c\u2010Myc\u2010dependent transactivation of survivin as a novel pathway in the transcriptional network orchestrated by BCR\/ABL. These results suggest that the interference with this circuitry might be a potential utility for CML treatment.<\/jats:p>","DOI":"10.1111\/j.1582-4934.2008.00549.x","type":"journal-article","created":{"date-parts":[[2008,10,13]],"date-time":"2008-10-13T12:00:14Z","timestamp":1223899214000},"page":"2039-2052","source":"Crossref","is-referenced-by-count":34,"title":["Transcriptional regulation of survivin by c\u2010Myc in BCR\/ABL\u2010transformed cells: implications in anti\u2010leukaemic strategy"],"prefix":"10.1111","volume":"13","author":[{"given":"Zhi Hong","family":"Fang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun 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