Molecular pathogenesis of leukemia by the GATA1 gene mutation
| Project/Area Number |
17K10094
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Hirosaki University |
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Principal Investigator |
Kanezaki Rika 弘前大学, 医学研究科, 助教 (60722882)
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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 |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 転写因子 / 白血病 |
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| Outline of Final Research Achievements |
Approximately 10% of newborns with Down Syndrome develop transient abnormal myelopoiesis (TAM). TAM has a high rate of early mortality and a high risk of progression to acute megakaryoblastic leukemia (ML-DS). The purpose of this study is to elucidate the molecular pathogenesis and the mechanism of cell proliferation of TAM.
In almost of all TAM and ML-DS, mutations of the GATA1 gene, essential for megakaryocytic differentiation are detected. These mutations lead to the expression of proteins lacking the N-terminus (GATA1s). In this study, we investigated the expression regulation mechanism of the receptor tyrosine kinase KIT gene that promotes cell proliferation of blast cells of TAM. We revealed that GATA1s-induced conformational changes in the genome lead to increased expression of the KIT gene.
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| Academic Significance and Societal Importance of the Research Achievements |
TAMにおけるKIT遺伝子の過剰発現が、なぜ、どのようにして引き起こされているのか発現制御メカニズムを解明することは、TAMの発症機構を解明する上で重要であり、KITを標的とした治療法を実用化する際に必要な知見である。また、本来転写活性化因子であるGATA1がKITの転写を抑制し、逆に転写活性化領域であるN末端を欠くGATA1sがGATA1にとって代わることでKITの発現が増加する、という興味深い現象に対してKIT遺伝子の発現制御モデルを示すことができ、基礎的な分子生物学の分野にも貢献しうる研究成果が得られたものと考える。
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Report
(4 results)
Research Products
(3 results)
