Determinants of Oncogenic Transformation in Acute Promyelocytic Leukemia: The Hetero-Union Makes the Force

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• 作者：Saverio Minucci ; Pier Giuseppe Pelicci
• 关键词：CELLCYCLE
• 刊名：Cancer Cell
• 出版年：2007
• 出版时间：10 July 2007
• 年：2007
• 卷：12
• 期：1
• 页码：1-3
• 全文大小：87 K

文摘

Cancer cells exhibit many abnormal phenotypes that induce apoptotic signaling via the intrinsic, or mitochondrial, pathway. That cancer cells nonetheless survive implies that they select for blocks in apoptosis. Identifying cancer-specific apoptotic blocks is necessary to rationally target them. Using a panel of 18 lymphoma cell lines, we show that a strategy we have developed, BH3 profiling, can identify apoptotic defects in cancer cells and separate them into three main classes based on position in the apoptotic pathway. BH3 profiling identifies cells that require BCL-2 for survival and predicts sensitivity to the BCL-2 antagonist ABT-737. BCL-2 dependence correlates with high levels of proapoptotic BIM sequestered by BCL-2. Strikingly, BH3 profiling can also predict sensitivity to conventional chemotherapeutic agents like etoposide, vincristine, and adriamycin.