| Project/Area Number |
18K19463
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 50:Oncology and related fields
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| Research Institution | Tohoku University |
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Principal Investigator |
Suzuki Mikiko 東北大学, 医学系研究科, 講師 (80508309)
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| Project Period (FY) |
2018-06-29 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2019: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2018: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
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| Keywords | 白血病 / 染色体転座 / 染色体逆位 / EVI1 / MECOM / GATA2 / 原がん遺伝子 / 分化 / エピゲノム |
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| Outline of Final Research Achievements |
By monitoring EVI1 gene expression under the control of inv(3) allele, we found that the EVI1 gene is expressed not only in hematopoietic stem and progenitor cells but also in megakaryocyte lineage, which promotes megakaryocyte-lineage skewing. In addition to EVI1 gene expression, the down-regulation of the GATA2 gene caused by inv(3) promoted the development of leukemia with megakaryocyte hyperplasia, similar to leukemia of human patients. These results indicate that these EVI1 and GATA2 misexpression contribute to the development of leukemia caused by chromosome 3 inversion.
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| Academic Significance and Societal Importance of the Research Achievements |
3番染色体転座および逆位は、急性骨髄性白血病の約1-2%にみられる。3番染色体転座・逆位を伴う白血病に対する有効な治療法は確立されておらず、患者の予後は極めて不良である。本研究ではこの白血病発症モデルを樹立し、発症機構の一端を明らかにした。3番染色体転座および逆位を伴う白血病のモデルマウスとして、ヒト3番染色体転座・逆位を伴う白血病にみられる巨核球増多を再現できているのは、本モデルマウスのみであり、このマウスを用いた解析により、今後、さらに詳細な発症機構が明らかになると期待される。
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