2021 Fiscal Year Final Research Report
Immune evasion of AML cells from FceRI+ cells through MEIS1 activity
| 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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| Keywords | Acute Myeloid Leukemia / Meis1 / Immune evasion / Oncology |
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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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| Free Research Field |
Leukemogenesis
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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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