2011 Fiscal Year Final Research Report

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

Research Project

Project/Area Number	22790919
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Single-year Grants
Research Field	Hematology
Research Institution	Keio University
Principal Investigator	ISHIZAWA Jo 慶應義塾大学, 医学部, 助教 (60445260)
Project Period (FY)	2010 – 2011
Keywords	血液腫瘍学
Research Abstract	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.