Infection stresses promote the pathogenesis of myelodysplastic syndrome
| Project/Area Number |
18H02842
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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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| Review Section |
Basic Section 54010:Hematology and medical oncology-related
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| Research Institution | Kumamoto University |
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Principal Investigator |
Sashida Goro 熊本大学, 国際先端医学研究機構, 特別招聘教授 (70349447)
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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 |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2019: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2018: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
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| Keywords | 骨髄異形成症候群 / 感染症 / クローン造血 / ゲノム変異 / エピゲノム / クロマチン / 老化 / DNAメチル化 / TET２ / クローナル造血 / ストレス / 造血幹細胞 / TET2 / クロナール造血 / 感染ストレス / 感染 |
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| Outline of Final Research Achievements |
Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disease of aged adults characterized by impaired hematopoiesis and predisposition to acute myeloid leukemia. By utilizing our infection stress-induced Tet2-deficient MDS model, we will understand the mechanism of how hematopoietic stem cells promote the initiation and propagation of MDS due to stem cells heterogeneity in epigenetic changes and impaired homeostasis in hematopoietic and non-hematopoietic tissues upon the insults of infection stresses. Lastly, we will clarify the molecular mechanism of pathogenesis of MDS and give a rationale for novel therapeutic strategy for the prevention of and eradication of MDS cells.
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| Academic Significance and Societal Importance of the Research Achievements |
加齢が慢性疾患やがんの発症をもたらすと信じられているが、複雑な生体内の生物学的応答のうちで、何が老化に伴ってがんになる原因であるかは不明である。本研究成果が進展することで、加齢幹細胞また前がん幹細胞が、感染罹患で生じたエピゲノム変化を蓄積・継承してMDS発症に至る分子基盤を理解できる。
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Report
(4 results)
Research Products
(23 results)
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[Journal Article] Lineage-specific RUNX2 super-enhancer activates MYC via a chromosomal translocation and promotes the development of blastic plasmacytoid dendritic cell neoplasm2019
Author(s)
Kubota S, Tokunaga K, Umezu T, Yokomizo-Nakano T, Oshima M, Tan KT, Yang H, Kanai A. Iwanaga E, Asou N, Maeda T, Nakagata N. Ito T, Iwama A. Ohyashiki K, Osato M, Sashida G.
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Journal Title
Nat Commun
Volume: 10
Issue: 1
Pages: 1653-1653
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Ezh1 Targets Bivalent Genes to Maintain Self-Renewing Stem Cells in Ezh2-Insufficient Myelodysplastic Syndrome.2018
Author(s)
Aoyama K, Oshima M, Koide S, Suzuki E, Mochizuki-Kashio M, Kato Y, Tara S, Shinoda D, Hiura N, Nakajima-Takagi Y, Sashida G, Iwama A.
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Journal Title
iScience
Volume: 9
Pages: 161-174
DOI
Related Report
Peer Reviewed / Open Access
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