Pathogenesis of hypoplastic leukemia in murine models

• Project/Area Number: 15K19546
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: The University of Tokyo
• Principal Investigator: Arai Shunya 東京大学, 医学部附属病院, 講師 (00579716)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: Runx1 / 白血病 / 骨髄系腫瘍 / 炎症

Outline of Final Research Achievements

I transplanted murine hematopoietic progenitor cells (HPCs) transduced with the C-terminus truncated Runx1 mutant as a possible murine model of hypoplastic leukemia. However, the recipient mice have not developed leukemia. Then I constructed several CRISPR/Cas9 vectors that targeted the genomic locus of murine Runx1, and transduced murine HPCs with them. The HPCs expressing truncated Runx1 mutants were assayed by replating in cytokine-rich semisolid culture. In a result, the HPCs with truncated Runx1 mutants have not showed tumorigenic phenotypes such as survival advantage and differentiation block.