| Project/Area Number |
17H04211
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
森下 総司 順天堂大学, 医学部, 助教 (10635866)
荒木 真理人 順天堂大学, 医学(系)研究科(研究院), 先任准教授 (80613843)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2019: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
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| Keywords | 骨髄増殖性腫瘍 / iPS細胞 / JAK2V617F変異 / CRISPR/Cas9 / JAK2 / iPS / ゲノム編集 / 網羅的遺伝子解析 / 家族性骨髄増殖性腫瘍 / ドライバー遺伝子 / 骨髄線維症 / 急性白血病 / 遺伝子 / 癌 / 細胞 / ゲノム |
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| Outline of Final Research Achievements |
Philadelphia negative myeloproliferative neoplasms (MPN) are clonal disorders characterized by an overproduction of terminally differentiated hematopoietic cells. A majority of patients with MPN harbor JAK2V617F mutation, which is though as a driver gene mutation. Despite of several studies using mouse models and cell lines that link the JAK2V617F mutation and MPN, it was ambiguous whether JAK2V617F mutation alone was sufficient for the presentation of MPN phenotypes such as overproduction of terminally differentiated hematopoietic cells. In this study, we employed iPS cells derived from a healthy donor, introduced JAK2V617F mutation into these iPS cells, and demonstrated that the JAK2V617F alone was sufficient to induce MPN phenotypes in vitro.
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| Academic Significance and Societal Importance of the Research Achievements |
健常人から作ったiPS細胞にJAK2V617F変異を導入したところ、骨髄増殖性腫瘍患者でみられる造血能の亢進を、iPS細胞でも観察することができ、このiPS細胞を用いてJAK2V617F遺伝子の役割を解析することに成功した。このことから、今後はこのiPS細胞を用いて、新たな治療法の開発や病態解明がすすめられることから、その学術的意義、社会的意義は大きいと考える。
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