SIRT1 regulates metabolism and leukemogenic potential in CML stem cells
作者: Ajay AbrahamShaowei QiuBalu K ChackoHui LiAndrew PatersonJianbo HePuneet AgarwalMansi ShahRobert WelnerVictor M Darley-UsmarRavi Bhatia
刊名: Journal of Clinical Investigation, 2019, Vol.129 (7), pp.2685-2701
来源数据库: ProQuest Journal
原始语种摘要: Chronic myeloid leukemia (CML) results from hematopoietic stem cell transformation by the BCR-ABL kinase. Despite the success of BCR-ABL tyrosine kinase inhibitors (TKIs) in treating CML patients, leukemia stem cells (LSCs) resist elimination and persist as a major barrier to cure. Previous studies suggest that overexpression of the sirtuin 1 (SIRT1) deacetylase may contribute to LSC maintenance in CML. Here, by genetically deleting SIRT1 in transgenic CML mice, we definitively demonstrated an important role for SIRT1 in leukemia development. We identified a previously unrecognized role for SIRT1 in mediating increased mitochondrial oxidative phosphorylation in CML LSCs. We showed that mitochondrial alterations were kinase independent and that TKI treatment enhanced inhibition of CML...
全文获取路径: ProQuest  (合作)
影响因子:12.812 (2012)

  • CML Common Mode Logic
  • leukemogenic 引起白血病的
  • potential 
  • leukemia 白血病
  • hematopoietic 补血药
  • metabolism 代谢
  • hematopoiesis 红细胞生成作用
  • ABL Automatic Bootstrap Loader
  • definitively 确定的
  • deacetylase 脱乙酰基酶