Phenomic Screen to Explore Novel Pathogenesis of Leukemia Using PSC-Derived Hematopoietic Cells

2014 Fiscal Year Final Research Report

• Project/Area Number: 25860856
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Kyoto University
• Principal Investigator: NIWA Akira 京都大学, iPS細胞研究所, 助教 (20546999)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 白血病 / 造血発生 / ＥＳ／ｉＰＳ細胞

Outline of Final Research Achievements

To elucidate unknown pathogenesis of AML1-ETO (AE) gene in luekemia, we induced hematopoietic cells from PSCs harbouring inducible AE fusion gene cassettes with or without other pathogenic genes such as RTK mutations, and performed in vitro and in vivo assay. First, serial replanting assays in methylcellulose-containing semisolid media as well as liquid culture revealed the strong tendency toward increased colony forming efficacy and suppressed differentiation. In addition to in vitro assays, we next evaluated the in vivo phenotype by transplanting hematopoietic cells into immunodeficient NOG mice. Also in these experiments, we successfully observed the cooperation between AE and RTK mutations for increased engraftment with leukemia-like phenotypes when transplanting immature HSPCs. Those results indicated the successful recapitulation of pathogenic cooperation between AE and RTK mutations in our PSC-derived hematopoietic cells.

Free Research Field

小児科学