| Project/Area Number |
18K07182
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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 49070:Immunology-related
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| Research Institution | Nara Medical University (2019-2020)
Tokyo University of Science (2018) |
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Principal Investigator |
Oda Akihisa 奈良県立医科大学, 医学部, 特任助教 (80547703)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 脾臓微小環境 / Tlx1 / 脾臓髄外造血 / 骨髄性増殖疾患 / 白血病ニッチ / 間葉系細胞 / 間葉系幹細胞 / 骨髄性白血病 / 脾腫 / 脾臓 / 髄外造血 / 骨髄性白血病hakketubyou / 造血幹細胞 / ニッチ / 間葉系前駆細胞 |
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| Outline of Final Research Achievements |
Splenic extramedullary hematopoiesis (EMH) is induced by infection, chronic inflammation, and leukemia. Previously, the we showed that the regulation of Tlx1 expression in splenic mesenchymal progenitor cells directly regulates EMH.
However, whether there are some specific pathophysiological roles of spleen microenvironment in hematopoietic malignancies are largely unknown. In this study, we found that mice that keep to overexpress Tlx1 specifically in splenic mesenchymal progenitor cells exhibited leukemia-like symptoms with monocyte infiltration into the liver and lungs. Although EMH in the spleen was previously thought to be a secondary pathological process in chronic diseases so far, we showed here that the splenic microenvironment can provide the suitable micro-environment (a leukemic niche) for leukemic cells by the upregulation of Tlx1, leading to leukemia development and bad prognosis.
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| Academic Significance and Societal Importance of the Research Achievements |
これまで脾臓髄外造血は慢性疾患の二次的な病態であるとの認識であったが、長期にわたる慢性的な脾臓髄外造血、すなわち脾臓髄外造血制御の破綻は、骨髄増殖疾患の発症に関与している事を明らかにした。またTlx1を発現上昇した脾臓微小環境は、造血制御因子の増加を伴う白血病ニッチへと変化し、白血病の病態悪化に直接的に関与している事を明らかにした。さらに明らかにするべきは、白血病細胞がTlx1発現を上昇させるシグナルを同定し、脾臓ニッチと骨髄造血ニッチとの間の相互作用メカニズムについて追求する事である。これらの研究を継続し完遂できる環境を再度得られる様に努力したい。
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