Research for regulatory mechanisms of normal hematopoietic stem cell and leukemia stem cell pool via mTOR Complex 1

mTOR复合物1对正常造血干细胞和白血病干细胞库的调节机制研究

• 批准号: 22790906
• 负责人: HOSHII Takayuki
• 金额: $ 2.58万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22790906/
• 关键词: 幹細胞; シグナル伝達; mTOR複合体

Although dysregulation of mTOR complex 1(mTORC1) promotes leukemogenesis, how mTORC1 affects established leukemia is unclear. We investigated the role of mTORC1 in mouse model of acute myeloid leukemia. Raptor deficiency significantly suppressed leukemia progression by causing apoptosis of differentiated, but not undifferentiated, leukemia cells. Strikingly, a subset of AML cells with undifferentiated phenotypes survived long-term in the absence of mTORC1 activity. Thus, AML cells lacking mTORC1 activity can self-renew as AML stem cells.

虽然mTOR复合物1（mTORC1）的失调促进白血病发生，但mTORC1如何影响已建立的白血病尚不清楚。我们研究了mTORC 1在小鼠急性髓系白血病模型中的作用。Raptor缺陷通过引起分化的而非未分化的白血病细胞凋亡而显著抑制白血病进展。令人惊讶的是，一个具有未分化表型的AML细胞亚群在缺乏mTORC1活性的情况下长期存活。因此，缺乏mTORC 1活性的AML细胞可以自我更新为AML干细胞。