• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nature cancer. >Mitochondrial inhibitors circumvent adaptive resistance to venetoclax and cytarabine combination therapy in acute myeloid leukemia
【24h】

Mitochondrial inhibitors circumvent adaptive resistance to venetoclax and cytarabine combination therapy in acute myeloid leukemia

机译：线粒体抑制剂规避适应性抵抗venetoclax和阿糖胞苷联合治疗在急性髓系白血病

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Therapy resistance represents a major clinical challenge in acute myeloid leukemia (AMD. Here we define a 'MitoScore' signature, which identifies high mitochondrial oxidative phosphorylation in vivo and in patients with AML. Primary AML cells with cytarabine (AraC) resistance and a high MitoScore relied on mitochondrial Bcl2 and were highly sensitive to venetoclax (VEN) + AraC (but not to VEN + azacytidine). Single-cell transcriptomics of VEN + AraC-residual cell populations revealed adaptive resistance associated with changes in oxidative phosphorylation, electron transport chain complex and the TP53 pathway. Accordingly, treatment of VEN + AraC-resistant AML cells with electron transport chain complex inhibitors, pyru-vate dehydrogenase inhibitors or mitochondrial CIpP protease agonists substantially delayed relapse following VEN + AraC. These findings highlight the central role of mitochondrial adaptation during AML therapy and provide a scientific rationale for alternating VEN + azacytidine with VEN + AraC in patients with a high MitoScore and to target mitochondrial metabolism to enhance the sensitivity of AML cells to currently approved therapies.
机译：代表一个主要临床治疗阻力在急性髓系白血病(AMD的挑战。定义一个“MitoScore”签名,标识高线粒体氧化磷酸化体内和AML患者。与阿糖胞苷(AraC)电阻和高MitoScore依靠线粒体Bcl2和高度敏感venetoclax (VEN) + AraC(但不要VEN + azacytidine)。转录组VEN + AraC-residual细胞数量显示自适应抗与氧化的变化有关电子传递链磷酸化,复杂和TP53的途径。与电子VEN + AraC-resistant AML细胞传递链复杂的抑制剂,pyru-vate脱氢酶抑制剂或CIpP线粒体蛋白酶受体激动剂显著延迟复发后VEN + AraC。线粒体适应的核心作用在AML治疗和提供科学理由交替VEN + azacytidineVEN + AraC高MitoScore和患者针对线粒体代谢增强灵敏度的AML细胞目前批准疗法。

著录项

相似文献

  • 外文文献
  • 中文文献
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号