诱导细胞周期进入可消除 AML 小鼠模型中的人类白血病干细胞。
Induction of cell cycle entry eliminates human leukemia stem cells in a mouse model of AML.
机构信息
Research Unit for Human Disease Models, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan.
出版信息
Nat Biotechnol. 2010 Mar;28(3):275-80. doi: 10.1038/nbt.1607. Epub 2010 Feb 14.
Cancer stem cells have been proposed to be important for initiation, maintenance and recurrence of various malignancies, including acute myeloid leukemia (AML). We have previously reported that CD34+CD38- human primary AML stem cells residing in the endosteal region of the bone marrow are relatively chemotherapy resistant. Using a NOD/SCID/IL2rgamma(null) mouse model of human AML, we now show that the AML stem cells in the endosteal region are cell cycle quiescent and that these stem cells can be induced to enter the cell cycle by treatment with granulocyte colony-stimulating factor (G-CSF). In combination with cell cycle-dependent chemotherapy, G-CSF treatment significantly enhances induction of apoptosis and elimination of human primary AML stem cells in vivo. The combination therapy leads to significantly increased survival of secondary recipients after transplantation of leukemia cells compared with chemotherapy alone.
癌症干细胞被认为对各种恶性肿瘤的发生、维持和复发很重要，包括急性髓系白血病（AML）。我们之前曾报道过，骨髓骨内膜区域中存在的 CD34+CD38-人原发性 AML 干细胞对化疗具有相对抗性。使用 NOD/SCID/IL2rgamma(null) 人 AML 小鼠模型，我们现在表明，骨内膜区域中的 AML 干细胞处于细胞周期静止状态，并且这些干细胞可以通过粒细胞集落刺激因子（G-CSF）处理诱导进入细胞周期。与细胞周期依赖性化疗联合使用，G-CSF 处理可显著增强体内人原发性 AML 干细胞的凋亡诱导和消除。与单独化疗相比，联合治疗可导致白血病细胞移植后二次受体的生存率显著提高。
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