Study on isolation, characteristic and distribution of pediatric leukemic stem cell using NOG mouse model

NOG小鼠模型研究小儿白血病干细胞的分离、特性和分布

• 批准号: 21790983
• 负责人: FUJINO Hisanori
• 金额: $ 2.75万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21790983/
• 关键词: NOGマウス; 白血病幹細胞; 小児白血病; 幹細胞

Primary samples from patients with leukemia were successfully engrafted into mice, and those engrafted leukemic cells were able to be serially transplanted into secondary, tertiary recipients. Morphological and FACS analyses revealed as high as >80% blood chimerism and conserved blast phenotypes through serial transplantations. Moreover, extramedullary organs including liver, spleen and kidney showed the leukemic invasion consistent with donor disease. Immunohistological analysis of liver revealed that SDF-1 was detectable only in bile duct epithelial cells. In addition, we demonstrated directly the effect of SDF-1/CXCR4 axis in our model by using the CXCR4 inhibitor both in vivo and in vitro. Our study on the involvement of SDF-1/CXCR4 axis in liver could rink to the novel therapies which target the extramedullary sites in order to perfectly overcome leukemia.

来自白血病患者的原代样本成功地移植到小鼠中，并且这些移植的白血病细胞能够连续移植到第二、第三受体中。形态学和流式细胞术分析显示，通过连续移植，高达>80%的血液嵌合体和保守的原始细胞表型。此外，髓外器官包括肝、脾和肾显示白血病侵袭与供体疾病一致。肝脏的免疫组织化学分析显示SDF-1仅在胆管上皮细胞中可检测到。此外，我们通过使用CXCR 4抑制剂在体内和体外直接证明了SDF-1/CXCR 4轴在我们的模型中的作用。我们对SDF-1/CXCR 4轴在肝脏中的作用的研究可能有助于寻找靶向髓外部位的新疗法，从而更好地治疗白血病。

项目成果

Establishment of a Novel CNS Infiltrated Xenograft Model through Engraftment of Patient-Derived Acute Lymphoblastic Leukemic Cells Into NOD/SCID/γc^<Null> Mouse

通过将患者来源的急性淋巴细胞白血病细胞植入 NOD/SCID/γc^<Null> 小鼠中建立新型中枢神经系统浸润异种移植模型

• 发表时间: 2010
• 作者: Toki T;Fujino H;et al;加藤格
• 通讯作者: 加藤格

Selective infection of CD4+ effector memory T lymphocytes leads to preferential depletion of memory T lymphocytes in R5 HIV-1-infected humanized NOD/SCID/IL-2Rgammanull mice.

CD4效应记忆T淋巴细胞的选择性感染导致R5 HIV-1感染的人源化NOD/SCID/IL-2Rgammanull小鼠中记忆T淋巴细胞的优先消耗。

• 发表时间: 2009
• 期刊: Virology. 394
• 作者: Nie C;Fujino H;et al
• 通讯作者: et al

Blockage of SDF-1-CXCR4 Axis by AMD 3100 Can Be a Novel Therapy for Acute Lymphoblastic Leukemia by Targeting the Extramedullary Sites of Leukemic Cells.

AMD 3100 阻断 SDF-1-CXCR4 轴可以通过靶向白血病细胞的髓外部位成为急性淋巴细胞白血病的一种新疗法。

• 发表时间: 2009
• 作者: 加藤格、藤野寿典;他
• 通讯作者: 他

The key role of stem cell factor/KIT signaling in the proliferation of blast cells from Down syndrome-related leukemia

干细胞因子/KIT信号传导在唐氏综合症相关白血病母细胞增殖中的关键作用

• 发表时间: 2009
• 期刊: Leukemia 23
• 作者: Toki T;Ito E;et al.
• 通讯作者: et al.

Blockageof SDF-1-CXCR4 Axis by AMD 3100 Can Be a Novel Therapy for Acute Lymphoblastic Leukemia by Targeting the Extramedullary Sites of Leukemic Cells.

AMD 3100 阻断 SDF-1-CXCR4 轴可以通过靶向白血病细胞的髓外部位成为急性淋巴细胞白血病的一种新疗法。

• 发表时间: 2009
• 作者: Itaru Kato;Hisanori Fujino;他
• 通讯作者: 他