| Project/Area Number |
17H04210
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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 | University of Miyazaki |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
久冨木 庸子 宮崎大学, 医学部, 講師 (00284836)
幣 光太郎 宮崎大学, 医学部, 助教 (20468028)
日高 智徳 宮崎大学, 医学部, 講師 (40381115)
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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 |
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2019: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2017: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
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| Keywords | 骨髄線維症 / fibrocyte / シグナル伝達 / 骨髄増殖性腫瘍 / 癌 |
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| Outline of Final Research Achievements |
Elucidation of the pathophysiology of myeloproliferative neoplasms (MPNs) has been greatly advanced by the identification of the driver mutations JAK2 and CALR. On the other hand, the mechanism by which CALR mutations cause MPN and the mechanism of fibrosis, which is the most important feature of myelofibrosis, remain unclear.
We elucidated the role of CALR in normal hematopoiesis and the mechanism of clonal expansion of CALR-mutated aberrant hematopoietic stem cells. We also found that the majority of collagen-producing cells in the bone marrow, which are the main players in fibrosis, are neoplastic fibrocytes that differentiate from tumor clones via monocytes.
These are major achievements that promote the understanding of the pathogenesis of MPN, leading to the development of new treatment methods that meet unmet needs of patients.
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| Academic Significance and Societal Importance of the Research Achievements |
骨髄増殖性腫瘍(MPN)の有病率は血液腫瘍性疾患の中でも高く、患者は慢性的な随伴症状や重症化した病態である骨髄線維症への進展に苦しんでいる。本研究により、MPNの主要なドライバー変異であるCALR変異がMPNを発症させる機序について、未解明の疑問に答える大きな知見を示すことができた。また、骨髄線維化の本態であるコラーゲン産生細胞のほとんどが、腫瘍性単球由来のfibrocyteであるという従来の定説を覆す知見も示すことができた。これらの成果は、学術的には病態解明の歩みに大きな一歩を刻むものであり、社会的にはアンメットニーズに応えMPNの発症・進展を食い止める革新的治療開発の礎となる成果である。
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