Computational leukemic stem cell models in systems biology for analyses of cell kinetics in leukemic relapse and development of risk-stratified chemotherapy

Research Project

Project/Area Number	24591562
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Pediatrics
Research Institution	Kanazawa Medical University
Principal Investigator	SAIKAWA Yutaka 金沢医科大学, 医学部, 教授 (60283107)
Co-Investigator(Kenkyū-buntansha)	KOMATSUZAKI Toshihiko 金沢大学, 機械工学系, 准教授 (80293372)
Project Period (FY)	2012-04-01 – 2015-03-31
Project Status	Completed (Fiscal Year 2014)
Budget Amount *help	¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000) Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords	急性骨髄性白血病 / コンピューターシミュレーション / 白血病幹細胞 / システム生物学 / 微小残存病変 / コンピュータシミュレーション / 白血病治療モデル / 白血病造血モデル
Outline of Final Research Achievements	We have constructed a 3-dimentional computer simulation system to investigate the mechanisms of leukemic relapse and develop new risk-stratified treatment protocols. Comparing the cell kinetics of normal hemopoietic stem cells and leukemic stem cells, models of developing leukemias were successfully simulated from a single leukemic stem cells when the cell kinetics of leukemic stem cells was more than 3 times slower than normal hematopoietic stem cells. Subsequently, introducing simulations of chemotherapy, adapted from the AML-05 protocol from Japan Pediatric Leukemia Lymphoma Study Group, into our leukemic models has established a treatment model with 10-year relapse-free survival as a prototype.