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

我们分析了细胞周期调节因子Cdh1在造血系统中的作用，重点研究了Cdh1与恶性肿瘤细胞分化/假分化的关系。我们构建了Cdh1条件基因诱捕小鼠，其中Cdh1在造血细胞中特异性下调，并证明了Cdh1缺乏导致造血细胞对基因毒性应激的脆弱性。从其在血液系统恶性肿瘤中的作用来看，我们在B细胞急性淋巴细胞白血病/淋巴瘤（B- all /LBL）模型小鼠中也观察到Cdh1缺乏导致细胞脆性的现象。此外，我们发现继发性和三期cdh1缺失的B-ALL/LBL小鼠的预后往往比cdh1完整的小鼠差，这与原发性B-ALL/LBL小鼠的结果相反。

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.