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

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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.