Molecular characterization of ROCK leukemia between leukemia cells and endothelial cells in CNS leukemia

• Project/Area Number: 16K21176
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology; Pediatrics
• Research Institution: Shimane University
• Principal Investigator: Onishi Chie 島根大学, 学術研究院医学・看護学系, 助教 (30598115)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: FLT3-ITD / 白血病 / ROCK / FLT3阻害剤 / 治療抵抗性 / ROCK1 / ITD-FLT3 / CXCL12 / ULBP1

Outline of Final Research Achievements

FLT3 inhibitor-resistant cells were generated by prolonged dose-escalation exposure to quizartinib and/or gilteritinib in FLT3-ITD+ Ba/F3 cells. Combination of Rho-kinase inhibitor, fasudil and FLT3 inhibitor (quizartinib or gilteritinib) reduced proliferation of FLT3 inhibitor-resistant FLT3-ITD+ Ba/F3 cells compared with the same cells treated with quizartinib or gilteritinib alone.

Academic Significance and Societal Importance of the Research Achievements

近年、FLT3阻害剤による白血病細胞の耐性化が問題視されている。今回の私たちの研究から、ROCK阻害剤が、FLT3-ITD陽性白血病細胞におけるFLT3阻害剤抵抗性を克服するの可能性が示唆された。