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

2015 Fiscal Year Annual Research Report

• Project/Area Number: 15H06037
• Research Institution: Tohoku University
• Principal Investigator: 于 磊 東北大学, 医学(系)研究科(研究院), 産学官連携研究員 (00760654)
• Project Period (FY): 2015-08-28 – 2017-03-31
• Keywords: Hematopoietic stem cell / Leukemia stem cell / GATA1 / Apoptosis

Outline of Annual Research Achievements

In our study of 2015 fiscal year, we carefully analyzed the physiological significance of erythroid and megakaryocytic master transcription factor GATA1 gene silencing in hematopoietic stem cell (HSC). We found that silencer loss of GATA1 locus in HSC exhausts the population of HSC by inducing its apoptosis. Consequently, the GATA1 over-expressed mice show severe anemia due to total HSC exhaustion.
By generating HSC specific and inducible Cre mice lines and crossing these mice with Dnmt1 flow allele, we found that DNMT1 is responsible for Gata1 gene silencing in HSC. Meanwhile, transcription factor GATA2 activates Gata1 gene expression in absence of Gata1 HSC silencer element which recruit DNMT1.

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

The current status followed the research plan at the beginning of the grant application.

Strategy for Future Research Activity

In research plan of 2016, we would try to rescue acute myeloid leukemia in mice model by over-expressing GATA1 in leukemia stem cells. We hypothesize that enhanced GATA1 in leukemia stem cells would lead to its apoptosis and improve the disease progress