...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cancer Cell >Mutational Cooperativity Linked to Combinatorial Epigenetic Gain of Function in Acute Myeloid Leukemia
【24h】

Mutational Cooperativity Linked to Combinatorial Epigenetic Gain of Function in Acute Myeloid Leukemia

机译：突变合作性与急性髓性白血病功能的组合表观遗传学增益有关

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

Specific combinations of acute myeloid leukemia (AML) disease alleles, including FLT3 and TET2 mutations, confer distinct biologic features and adverse outcome. We generated mice with mutations in Tet2 and Flt3, which resulted in fully penetrant, lethal AML. Multipotent Tet2(-/-); Flt3(ITD) progenitors (LSK CD48(+)CD150(-)) propagate disease in secondary recipients and were refractory to standard AML chemotherapy and FLT3-targeted therapy. Flt3(ITD) mutations and Tet2 loss cooperatively remodeled DNA methylation and gene expression to an extent not seen with either mutant allele alone, including at the Gata2 locus. Re-expression of Gata2 induced differentiation in AML stem cells and attenuated leukemogenesis. TET2 and FLT3mutations cooperatively induce AML, with a defined leukemia stem cell population characterized by site-specific changes in DNA methylation and gene expression.
机译：急性骨髓性白血病（AML）等位基因的特定组合（包括FLT3和TET2突变）具有独特的生物学特征和不良结局。我们生成了在Tet2和Flt3中具有突变的小鼠，这导致了完全渗透的致命AML。多能Tet2（-/-）; Flt3（ITD）祖细胞（LSK CD48（+）CD150（-））在继发接受者中传播疾病，并且对标准AML化疗和以FLT3为靶点的治疗均具有抵抗力。 Flt3（ITD）突变和Tet2丢失协同重塑DNA甲基化和基因表达，达到任何一个单独的突变等位基因（包括在Gata2基因座处）都看不到的程度。 Gata2的重新表达诱导AML干细胞分化并减弱白血病的发生。 TET2和FLT3突变可协同诱导AML，具有明确的白血病干细胞群体，其特征在于DNA甲基化和基因表达的位点特异性变化。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
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