Development of novel therapeutic strategy against myeloid leukemia by inducing leukemia stem cell differentiation

2016 Fiscal Year Final Research Report

• Project/Area Number: 15H06037
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: General medical chemistry
• Research Institution: Tohoku University
• Principal Investigator: YU Lei 東北大学, 医学系研究科, 産学官連携研究員 (00760654)
• Project Period (FY): 2015-08-28 – 2017-03-31
• Keywords: Gata1 gene regulation / Erythropoiesis / Apoptosis

Outline of Final Research Achievements

I identified the crucial mechanism of erythropoiesis initiation from hematopoietic stem and progenitor cells (HSPCs). By generating several lines of Gata1 bacterial artificial chromosome transgenic mice in which the HSPC specific silencer was deleted, I could be able to induce high level of Gata1 or CreERT2 expression in HSPCs. By using these mouse models as well as Dnmt1 conditional knockout allele, I found the demethylation of enhancers (which was methylated and repressed by the HSPC specific silencer) of erythroid master transcription factor GATA1, and therefore the gene activation, is the key of the initiation of red blood cell differentiation.

Free Research Field

医化学