Identification and in vivo analysis of human cancer stem cells

2014 Fiscal Year Final Research Report

• Project Area: Development of Novel Treatment Strategies Targeting Cancer Stem Cells
• Project/Area Number: 22130002
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyushu University
• Principal Investigator: AKASHI Koichi 九州大学, 医学(系)研究科(研究院), 教授 (80380385)
• Co-Investigator(Kenkyū-buntansha): CHIBA Shigeru 筑波大学, 医学医療系, 教授 (60212049)
• Project Period (FY): 2010-04-01 – 2015-03-31
• Keywords: 白血病幹細胞 / 異種移植

Outline of Final Research Achievements

To analyze the function of human cancer stem cells in vivo, the xenograft model that permits an efficient engraftment of human cells is necessary. Because the traditional IL-2Rγnull-NOD/SCID (NOG) mouse system is not sufficient for this purpose, we newly developed a B6.Rag2nullIL2RγnullSIRPANOD/NOD (BRGS) mouse line that possesses a macrophage tolerance based on a SIRPA polymorphism. By using this xenograft system, we have shown that self-renewing hematopoietic stem cells are primary target in the pathogenesis of human chronic lymphocytic leukemia. Furthermore, we demonstrated that T-cell immunoglobulin mucin-3 (TIM-3) is expressed on surface of self-renewing leukemic stem cells (LSCs) in acute myeloid leukemia (AML) and that TIM-3 and its ligand, galectin-9 (Gal-9), constitute an autocrine loop critical for human AML LSC development.

Free Research Field

幹細胞学