Investigation of the origin of clonal hematopoiesis in aplastic anemia
| Project/Area Number |
15K15361
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Hematology
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| Research Institution | Kyoto University |
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Principal Investigator |
OGAWA SEISHI 京都大学, 医学(系)研究科(研究院), 教授 (60292900)
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| Co-Investigator(Renkei-kenkyūsha) |
TAKAORI Akifumi 京都大学, 医学研究科, 教授 (20324626)
Nakao Shinji 金沢大学, 医薬保健研究域医学系, 教授 (70217660)
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| Project Period (FY) |
2015-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
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| Keywords | 血液内科学 / 血液免疫学 / 再生不良性貧血 / 体細胞変異 / 細胞障害性T細胞 / クローン性造血 |
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| Outline of Final Research Achievements |
Little is known about clonal architecture of aplastic anemia and its significance in the pathogenesis. In this study, we performed massive parallel sequencing to 439 cases with aplastic anemia and revealed the whole picture of genomic aberrations. Mutations were observed in 36% of the cases and biased to the 5genes; BCOR/BCORL1, PIGA, DNMT3A and ASXL1. Mutations in genes including DNMT3A and ASXL1, which are frequently observed in myeloid tumors, were associated with poor prognosis and showed pre-leukemic feature. In contrast, clones with BCOR, BCORL1 and PIGA mutations were associated with favorable outcome and exhibited tendency not to expand, which indicate the possibility that these clones could escape from the attack by cytotoxic T cells and acquire clonal advantage. These results yielded insights about the pathogenesis of aplastic anemia and early detection of mutated clones and intervention towards cases with these clones might improve the prognosis of aplastic anemia.
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Report
(2 results)
Research Products
(4 results)
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[Journal Article] Somatic Mutations and Clonal Hematopoiesis in Aplastic Anemia.2015
Author(s)
Yoshizato T, Dumitriu B, Hosokawa K, Makishima H, Yoshida K, Townsley D, Sato-Otsubo A, Sato Y, Liu D, Suzuki H, Wu CO, Shiraishi Y, Clemente MJ, Kataoka K, Shiozawa Y, Okuno Y, Chiba K, Tanaka H, Nagata Y, Katagiri T, Kon A, Sanada M, Scheinberg P, Miyano S, Maciejewski JP, Nakao S, Young NS, Ogawa S.
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Journal Title
N Engl J Med.
Volume: 373
Issue: 1
Pages: 35-47
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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