In vivo stem cell tracking of myeloproliferative disease and identification of novel molecular targets

2015 Fiscal Year Final Research Report

• Project/Area Number: 26860721
• 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: SATO TOMOHIKO 東京大学, 医学部附属病院, 研究員 (90553694)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 白血病幹細胞 / 白血病モデルマウス / 造血幹細胞 / 遺伝子変異

Outline of Final Research Achievements

In CMML-developed Evi1-GFP;Kras-mutant mice, no GFP(Evi1)-positive leukemia cells were detected.
Even after 20-month observation, Evi1-GFP;ASXL-mutant knock-in mice looked healthy with no apparent signs of acute myeloid leukemia or myelodysplastic syndrome. ASXL-mutant knock-in BM cells showed a skewed differentiation to myeloid lineage. ASXL-mutant knock-in BM cells had 2.3-times higher hematopoietic colony formation capacity and higher replating capacity up to five times. These cells had a similar BM reconstituting capacity to wild type BM cells (eight-month observation). Retroviral CML induction to ASXL-mutant knock-in BM cells showed no acceleration of CML development, but recipients with IDH1-mutant transduced ASXL-mutant knock-in BM cells had leukemia development with 10-month duration while ASXL-wild counterparts showed no leukemia so far.

Free Research Field

造血器悪性腫瘍