| Project/Area Number |
24390262
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Nagoya University |
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Principal Investigator |
KOJIMA Seiji 名古屋大学, 医学(系)研究科(研究院), 教授 (20313992)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Yoshiyuki 名古屋大学, 大学院医学系研究科, 准教授 (40432273)
嶋田 明 岡山大学, 大学病院, 講師 (70391836)
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| Co-Investigator(Renkei-kenkyūsha) |
SHIMADA Akira 岡山大学, 大学病院, 講師 (70391836)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥13,390,000 (Direct Cost: ¥10,300,000、Indirect Cost: ¥3,090,000)
Fiscal Year 2014: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2013: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2012: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
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| Keywords | 若年性骨髄単球性白血病 / 原因遺伝子 / 白血病幹細胞 / エピジェネティクス / エクソーム解析 / 若年型骨髄単球性白血病 / RASシグナル経路 / 全エクソーム解析 / SETBP1 / メチル化解析 |
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| Outline of Final Research Achievements |
Juvenile myelomonocytic leukemia (JMML) is an intractable pediatric myeloid malignancy, and the development of novel molecular target therapy is strongly warranted. Here, we analyzed 92 JMML patients with next-generation sequencing technique, and identified that patients with newly identified SETBP1 and JAK3 mutations as secondary genetic events showed inferior survival rates (Sakaguchi H, et al, Nature Genetics 2013).
In addition, we assessed the effects of tyrosine kinase inhibitor (Dasatinib) and MEK inhibitor (MEK162) for bone marrow mononuclear cells from JMML patients. Dasatinib and MEK162 are significantly suppressed the colony forming of JMML cells. Flowcytometry-based BrdU/SubG1 analysis revealed that these drugs significantly suppress cell proliferation and induce cell apoptosis. Our findings support that Dasatinib and MEK inhibitor would be promising agents for treatment of JMML patients.
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