Bcl2 对于小鼠白血病干细胞的发育和维持并非必需。
Bcl2 is not required for the development and maintenance of leukemia stem cells in mice.
机构信息
Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas/Universidad de Salamanca, Campus Miguel Unamuno sin número, 37007 Salamanca, Spain.
出版信息
Carcinogenesis. 2010 Jul;31(7):1292-7. doi: 10.1093/carcin/bgq062. Epub 2010 Mar 18.
Abstract
The existence of leukemia stem cells (LSCs) responsible for tumor maintenance has been firmly established. Therefore, therapeutic targeting of these LSCs may have a profound impact on cancer eradication. The anti-apoptotic protein Bcl2 has been proposed as a therapeutic target, but its role in LSC biology has not been investigated. In order to understand the role of Bcl2 in LSC generation and maintenance, we have taken advantage of our Sca1-BCRABLp210 mouse model of human chronic myeloid leukemia and bcl2 gene-targeted mice. This study provides genetic evidence that the inhibition of Bcl2 is not critical for the generation, selection or maintenance of the tumor initiating and maintaining cells in mice.
摘要
白血病干细胞（LSCs）负责肿瘤的维持，其存在已得到充分证实。因此，针对这些 LSCs 的治疗可能会对癌症的根除产生深远影响。抗凋亡蛋白 Bcl2 已被提议作为一种治疗靶点，但它在 LSC 生物学中的作用尚未得到研究。为了了解 Bcl2 在 LSC 生成和维持中的作用，我们利用我们的 Sca1-BCRABLp210 人慢性髓性白血病小鼠模型和 bcl2 基因靶向小鼠进行了研究。这项研究提供了遗传证据，表明抑制 Bcl2 对于小鼠中肿瘤起始和维持细胞的生成、选择或维持并非关键。
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2
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Cancer Cell. 2009 Feb 3;15(2):87-9. doi: 10.1016/j.ccr.2009.01.011.
3
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EMBO J. 2009 Jan 7;28(1):8-20. doi: 10.1038/emboj.2008.253. Epub 2008 Nov 27.
4
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