Role of MEIS1 in the immune evasion of myeloid leukemic cells

Research Project

Project/Area Number	16K18431
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Tumor biology
Research Institution	Japanese Foundation for Cancer Research
Principal Investigator	COUZINET Arnaud 公益財団法人がん研究会, がん研究所発がん研究部, 研究員 (70725621)
Project Period (FY)	2016-04-01 – 2018-03-31
Project Status	Completed (Fiscal Year 2017)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000) Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords	Acute Myeloid Leukemia / Immune evasion / Meis1 / Oncology / MEIS1 / Immune Evasion
Outline of Final Research Achievements	In acute myeloid leukemia, the transcription factor MEIS1 is critical for in vivo invasion and propagation of HOXA9-transformed leukemic cells. We previously showed that MEIS1 overexpression was critical for bone marrow engraftment of leukemic cells. However, we found that restoring engraftment capacity was not sufficient for leukemia onset to occur. Indeed, we found that leukemic cells are under immune attack in vivo but have the ability to escape this immune assault. We therefore hypothesized that MEIS1 was critical for immune evasion. This project led to the discovery that : (1) HOXA9-transformed cells are detected by FcεRI+ cells followed by eradication by T lymphocytes. (2) MEIS1 overexpression confers immune evasion capability to HOXA9-transformed leukemic cells by making cells insensitive to FcεRI+ cells.