| Budget Amount *help |
¥355,160,000 (Direct Cost: ¥273,200,000、Indirect Cost: ¥81,960,000)
Fiscal Year 2014: ¥56,940,000 (Direct Cost: ¥43,800,000、Indirect Cost: ¥13,140,000)
Fiscal Year 2013: ¥65,000,000 (Direct Cost: ¥50,000,000、Indirect Cost: ¥15,000,000)
Fiscal Year 2012: ¥67,990,000 (Direct Cost: ¥52,300,000、Indirect Cost: ¥15,690,000)
Fiscal Year 2011: ¥67,340,000 (Direct Cost: ¥51,800,000、Indirect Cost: ¥15,540,000)
Fiscal Year 2010: ¥97,890,000 (Direct Cost: ¥75,300,000、Indirect Cost: ¥22,590,000)
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| 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.
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