| Project/Area Number |
19K07678
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 50010:Tumor biology-related
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| Research Institution | National Cancer Center Japan (2020-2021)
Japanese Foundation for Cancer Research (2019) |
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Principal Investigator |
COUZINET Arnaud 国立研究開発法人国立がん研究センター, 先端医療開発センター, 特任研究員 (70725621)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | Acute Myeloid Leukemia / Meis1 / Immune evasion / Oncology / Immune Evasion |
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| Outline of Research at the Start |
This study will attempt to unveil the cellular dialogue between HOXA9/MEIS1-driven acute myeloid leukemic cells and immune cells (particularly FcεRI+ cells), and the MEIS1-regulated molecular dialogue between them.
Our preliminary results suggest that FcεRI+ cells (basophils and mast cells) have a dual role:
1) they secrete inhibitory factor(s) for leukemic cells,
2) they activate the adaptive immune system (T and/or B lymphocytes) for efficient leukemic cells eradication.
The role of MEIS1 in these two processes will be investigated.
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| Outline of Final Research Achievements |
Overexpression of the transcription factor HOXA9 is sufficient to immortalize hematopoietic stem cells in vitro, but co-overexpression of the transcription factor MEIS1 is necessary for in vivo invasion and propagation of HOXA9-transformed leukemic cells.
We previously showed that MEIS1 overexpression is critical for bone marrow engraftment of leukemic cells following in vivo injection. However, we unraveled that the sole engraftment capacity is 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 is critical for immune evasion. This project led to the discovery that: (1) HOXA9-transformed cells are detected by FcεRI+ cells (basophils and/or mast 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.
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| Academic Significance and Societal Importance of the Research Achievements |
This project helps understanding the mechanisms underlying the escape of leukemic cells from the immune defense system. It may lead to the development of either leukemia immunotherapeutic strategies or curative treatment aimed at annihilating the immune escape ability of leukemic cells.
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