CSC：协同响应基因调节白血病干细胞增殖和存活

白血病干细胞（LSCs）代表骨髓性白血病细胞中独特的一部分肿瘤细胞。它们细胞周期活性低，针对治疗的抵抗性强。为了更好地探究LSCs的主要特性，本研究基于不同癌基因之间的协同效应对白血病干细胞进行了综合分析。

研究者推测，被称为"协同响应基因（CRGs）"的一群基因可能调节LSCs的增长和存活。应用原代小鼠模型和人类白血病标本为研究对象，研究者发现，CRGs包括以往研究所没有发现的若干重要基因。这些基因在白血病发病过程的多种信号途径中调节LSCs的生物活性。

此外，研究结果还表明，CRG表达谱可用于作为药物开发的工具，研发选择性地针对LSCs亚群白血病细胞的化合物。

总之，以CRG为基础的分析，为阐明LSCs的生物学行为以及促进靶向治疗研发提供了强有力的手段。

doi:10.1016/j.cell.2011.10.017
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Gene Sets Identified with Oncogene Cooperativity Analysis Regulate In Vivo Growth and Survival of Leukemia Stem Cells

John M. Ashton, Marlene Balys, Sarah J. Neering, Duane C. Hassane, Glenn Cowley, David E. Root, Peter G. Miller, Benjamin L. Ebert, Helene R. McMurray, Hartmut Land, Craig T. Jordan

Leukemia stem cells (LSCs) represent a biologically distinct subpopulation of myeloid leukemias, with reduced cell cycle activity and increased resistance to therapeutic challenge. To better characterize key properties of LSCs, we employed a strategy based on identification of genes synergistically dysregulated by cooperating oncogenes. We hypothesized that such genes, termed cooperation response genes (CRGs), would represent regulators of LSC growth and survival. Using both a primary mouse model and human leukemia specimens, we show that CRGs comprise genes previously undescribed in leukemia pathogenesis in which multiple pathways modulate the biology of LSCs. In addition, our findings demonstrate that the CRG expression profile can be used as a drug discovery tool for identification of compounds that selectively target the LSC population. We conclude that CRG-based analyses provide a powerful means to characterize the basic biology of LSCs as well as to identify improved methods for therapeutic targeting.