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.

本文分析了细胞周期调控因子Cdh 1在造血系统中的作用，重点探讨了Cdh 1与恶性肿瘤细胞分化/假分化的关系。我们产生了Cdh 1条件基因陷阱小鼠，其中Cdh 1是下调，特别是在造血细胞，并证明Cdh 1缺陷导致造血细胞对遗传毒性应激的脆弱性。从其在血液恶性肿瘤中的作用的观点来看，我们经历了表明Cdh 1缺乏也在B细胞急性淋巴细胞白血病/淋巴瘤（B-ALL/LBL）模型小鼠中引起细胞脆性的现象。此外，还发现第二和第三Cdh 1缺陷型B-ALL/LBL小鼠的预后往往比Cdh 1完整型B-ALL/LBL小鼠更差，这与原发性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