2010 Fiscal Year Final Research Report

Study on isolation, characteristic and distribution of pediatric leukemic stem cell using NOG mouse model

Research Project

Project/Area Number	21790983
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Single-year Grants
Research Field	Pediatrics
Research Institution	Kyoto University
Principal Investigator	FUJINO Hisanori Kyoto University, 医学研究科, 助教 (70532604)
Project Period (FY)	2009 – 2010
Keywords	NOGマウス / 白血病幹細胞
Research Abstract	Primary samples from patients with leukemia were successfully engrafted into mice, and those engrafted leukemic cells were able to be serially transplanted into secondary, tertiary recipients. Morphological and FACS analyses revealed as high as >80% blood chimerism and conserved blast phenotypes through serial transplantations. Moreover, extramedullary organs including liver, spleen and kidney showed the leukemic invasion consistent with donor disease. Immunohistological analysis of liver revealed that SDF-1 was detectable only in bile duct epithelial cells. In addition, we demonstrated directly the effect of SDF-1/CXCR4 axis in our model by using the CXCR4 inhibitor both in vivo and in vitro. Our study on the involvement of SDF-1/CXCR4 axis in liver could rink to the novel therapies which target the extramedullary sites in order to perfectly overcome leukemia.