Analyzing the mechanism of cell differentiation in hematopoiesis through conditional gene-trap of the cell cycle regulator Cdh1.

通过细胞周期调节因子Cdh1的条件基因陷阱分析造血细胞分化机制。

• 批准号: 22790919
• 负责人: ISHIZAWA Jo
• 金额: $ 2.58万
• 依托单位: Keio 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-22790919/
• 关键词: 血液腫瘍学; 急性リンパ性白血病; 細胞周期; Cdh1; 遺伝子毒性ストレス; 細胞脆弱性; G2/Mチェックポイント; 造血

We analyzed the role of the cell cycle regulator Cdh1 in hematopoietic system, focusing on the relationship between Cdh1 and cell differentiation/pseudodifferentiation in malignancies. We generated Cdh1 conditional gene-trap mice in which Cdh1 is downregulated specifically in hematopoietic cells, and proved that Cdh1 deficiency causes hematopoietic cell fragility against genotoxic stress. From the point of view of its role in hematological malignancies, we experienced the phenomenon suggesting that Cdh1 deficiency cause cell fragility also in B cell acute lymphoblastic leukemia/lymphoma(B-ALL/LBL) model mice. Furthermore, it is found that secondary and tertiary Cdh1-deficient B-ALL/LBL mice tend to reveal poorer prognosis than Cdh1-intact ones, which is the opposite result from that of primary B-ALL/LBL mice.

我们分析了细胞周期调节分子CDH1在造血系统中的作用，重点阐述了CDH1与肿瘤细胞分化/假性分化的关系。我们建立了CDH1条件性基因陷阱小鼠，其中CDH1在造血细胞中特异性下调，并证明了CDH1缺乏导致造血细胞在遗传毒性应激下的脆性。从CDH1在血液系统恶性肿瘤中的作用来看，在B细胞急性淋巴细胞白血病/淋巴瘤(B-ALL/LBL)模型小鼠中，CDH1缺乏也会导致细胞脆性。此外，研究还发现，继发性和三级性CDH1缺陷的B-ALL/LBL小鼠的预后往往比CDH1完整的B-ALL/LBL小鼠更差，这一结果与初级B-ALL/LBL小鼠的结果相反。

项目成果

Role of the Cell Cycle Regulator Cdh1 in Physiology and Pathology of Hematopoiesis

细胞周期调节因子Cdh1在造血生理和病理中的作用

• 发表时间: 2011
• 作者: Ishizawa J;Kuninaka S;Sugihara E;Naoe H;Kobayashi Y;Chiyoda T;Ueki A;Araki K;Yamamura K;Matsuzaki Y;Nakajima H;Ikeda Y;Okamoto S and Saya H;石澤丈;石澤丈
• 通讯作者: 石澤丈

The cell cycle regulator Cdh1 controls the pool sizes of hematopoietic stem cells and mature lineage progenitors by protecting from genotoxic stress

• DOI: 10.1111/j.1349-7006.2011.01884.x
• 发表时间: 2011-05-01
• 期刊: CANCER SCIENCE
• 影响因子: 5.7
• 作者: Ishizawa, Jo;Kuninaka, Shinji;Saya, Hideyuki
• 通讯作者: Saya, Hideyuki