Clonal development of hematopoietic progenitor cells with driver mutation in myeloproliferative neoplasms
| Project/Area Number |
18K16120
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 54010:Hematology and medical oncology-related
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| Research Institution | Kurume University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 巨核球前駆細胞 / 本態性血小板増多症 / 骨髄増殖性腫瘍 / CHIP / ドライバー変異 / シングルセル / 巨核球系前駆細胞 / 腫瘍化メカニズム / JAK2変異 |
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| Outline of Final Research Achievements |
Recent studies revealed that driver mutations of hematologic malignancies could be found in white blood cells in healthy individuals, what we call “CHIP.” The existence of CHIP suggested that driver mutation itself is not sufficient, and some additional factors should be required for leukemogenesis. To address the background mechanisms of this, we analyzed JAK2 mutation clones in bone marrow from essential thrombocythemia patients and healthy individuals. We first identified prospectively-isolatable and functionally homogeneous human megakaryocyte progenitor. By performing comparative analysis in hematopoietic stem/progenitor populations, including MegP, we identified several key factors that potentially contribute to the acquisition of growth advantage for JAK2 mutant clones.
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| Academic Significance and Societal Importance of the Research Achievements |
CHIPの存在は昨今の血液学の発見の中でも極めてインパクトの大きいものであり、CHIPからの腫瘍化のメカニズムの解明は現在重要な課題となっている。すなわち、CHIPの獲得は加齢現象として避けることは難しいが、腫瘍化のメカニズムが解明されれば、CHIPの他にどのような因子を有している人間が腫瘍化しやすいのか、というリスク因子が明らかになり、腫瘍化に必要な因子を標的にすることで効果的な新規治療戦略開発が可能になる。このように、本研究内容は、腫瘍の病態メカニズムの解明にとどまらず、予防医学・治療医学など造血器腫瘍に対して多面的に貢献することが期待される。
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Report
(3 results)
Research Products
(1 results)
