Development of novel molecular targeted therapy for juvenile myelomonocytic leukemia
| 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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Report
(4 results)
Research Products
(54 results)
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[Journal Article] Aldehyde dehydrogenase-2 polymorphism contributes to the progression of bone marrow failure in children with idiopathic aplastic anaemia.2015
Author(s)
Kawashima N, Narita A, Wang X, Xu Y, Sakaguchi H, Doisaki S, Muramatsu H, Hama A, Nakanishi K, Takahashi Y, Kojima S.
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Journal Title
Br J Haematol.
Volume: 168
Pages: 460-463
DOI
Related Report
Peer Reviewed
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[Journal Article] RUNX1 mutation associated with clonal evolution in relapsed pediatric acute myeloid leukemia with t(16;21)(p11;q22).2014
Author(s)
Ismael O, Shimada A, Elmahdi S, Elshazley M, Muramatsu H, Hama A, Takahashi Y, Yamada M, Yamashita Y, Horibe K, Kojima S.
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Journal Title
Int J Hematol.
Volume: 99
Pages: 169-174
DOI
Related Report
Peer Reviewed
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[Journal Article] Long-term outcome after immunosuppressive therapy with horse or rabbit antithymocyte globulin and cyclosporine for severe aplastic anemia in children.2014
Author(s)
Jeong DC, Chung NG, Cho B, Zou Y, Ruan M, Takahashi Y, Muramatsu H, Ohara A, Kosaka Y, Yang W, Kim HK, Zhu X, Kojima S.
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Journal Title
Haematologica.
Volume: 99
Pages: 664-671
DOI
Related Report
Peer Reviewed
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[Journal Article] Peripheral blood lymphocyte telomere length as a predictor of response to immunosuppressive therapy in childhood aplastic anemia.2014
Author(s)
Sakaguchi H, Nishio N, Hama A, Kawashima N, Wang X, Narita A, Doisaki S, Xu Y, Muramatsu H, Yoshida N, Takahashi Y, Kudo K, Moritake H, Nakamura K, Kobayashi R, Ito E, Yabe H, Ohga S, Ohara A, Kojima S; Japan Childhood Aplastic Anemia Study Group.
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Journal Title
Haematologica.
Volume: 99
Pages: 1312-1316
DOI
Related Report
Peer Reviewed
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[Journal Article] Immunosuppressive therapy with horse anti-thymocyte globulin and cyclosporine as treatment for fulminant aplastic anemia in children.2014
Author(s)
Yagasaki H, Shichino H, Ohara A, Kobayashi R, Yabe H, Ohga S, Hamamoto K, Ohtsuka Y, Shimada H, Inoue M, Muramatsu H, Takahashi Y, Kojima S.
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Journal Title
Ann Hematol.
Volume: 93
Pages: 747-752
DOI
Related Report
Peer Reviewed
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[Journal Article] First-line treatment for severe aplastic anemia in children: bone marrow transplantation from a matched family donor versus immunosuppressive therapy.2014
Author(s)
Yoshida N, Kobayashi R, Yabe H, Kosaka Y, Yagasaki H, Watanabe K, Kudo K, Morimoto A, Ohga S, Muramatsu H, Takahashi Y, Kato K, Suzuki R, Ohara A, Kojima S
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Journal Title
Haematologica.
Volume: 99
Pages: 1784-1791
DOI
Related Report
Peer Reviewed
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[Journal Article] Spliceosomal gene mutations are frequent events in the diverse mutational spectrum of chronic myelomonocytic leukemia but largely absent in juvenile myelomonocytic leukemia.2013
Author(s)
Kar SA, Jankowska A, Makishima H, Visconte V, Jerez A, Sugimoto Y, Muramatsu H, Traina F, Afable M, Guinta K, Tiu RV, Przychodzen B, Sakaguchi H, Kojima S, Sekeres MA, List AF, McDevitt MA, Maciejewski JP.
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Journal Title
Haematologica
Volume: 98(1)
Pages: 107-113
DOI
Related Report
Peer Reviewed
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[Journal Article] Rabbit antithymocyte globulin and cyclosporine as first-line therapy for children with acquired aplastic anemia2013
Author(s)
Takahashi Y, Muramatsu H, Sakata N, Hyakuna N, Hamamoto K, Kobayashi R, Ito E, Yagasaki H, Ohara A, Kikuchi A, Morimoto A, Yabe H, Kudo K, Watanabe K, Ohga S, Kojima S
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Journal Title
Blood.
Volume: 121(5)
Pages: 862-3
DOI
Related Report
Peer Reviewed
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[Presentation] Generation of Cell Lines Harboring SETBP1 Mutations By the Crispr/Cas9 system2014
Author(s)
Kawashima N, Okuno Y, Sekiya Y, Wang X, Xu Y, Narita A, Doisaki S, Kamei M, Muramatsu H, Irie M, Hama A, Takahashi Y, Kojima S.
Organizer
56th ASH Annual Meeting and Exposition
Place of Presentation
San Francisco, USA
Year and Date
2014-12-08
Related Report
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[Presentation] Mutational analysis of RRAS in Japanese juvenile myelomonocytic leukemia patient2014
Author(s)
Wang X, Nishikawa E, Muramatsu H, Okuno Y, Sekiya Y, Kawashima N, Xu Y, Narita A, Doisaki S, Hama A, Takahashi Y, Kojima S.
Organizer
第56回日本小児血液・がん学会学術集会
Place of Presentation
岡山県岡山市（ 岡山コンベンションセンター）
Year and Date
2014-11-28
Related Report
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[Presentation] Clinical and genetic characterization of 17 Juvenile myelomonocytic leukemia patients with c-CBL mutations.
Author(s)
Muramatsu H, Sakaguchi H, Xu Y, Yoshida K, Okuno Y, Hama A, Takahashi Y, Makishima H, Maciejewski J.P, Ogawa S, Kojima S.
Organizer
The 12th International Symposium on Myelodysplastic Syndromes.
Place of Presentation
Berlin, Germany
Related Report
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[Presentation] Molecular Spectrum of Juvenile Myelomonocytic Leukemia Identified by Whole exome sequencing.
Author(s)
Sakaguchi H, Muramatsu H, Yoshida K, Okuno Y, Shiraishi Y, Sanada M, Chiba K, Tanaka H, Makishima H, Wang X, Xu Y, Doisak Si, Hama A, Nakanishi K, Takahashi Y, Yoshida N, Maciejewski JP, Miyano S, Ogawa S, Kojima S.
Organizer
The 18th Congress of EHA.
Place of Presentation
Stockholm, Sweden
Related Report
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[Presentation] Clinical and Genetic Characterization Of Patients With C-CBL Mutated Juvenile Myelomonocytic Leukemia By Whole-Exome/Deep Sequencing.
Author(s)
Muramatsu H, Sakaguchi H, Wang X, Yoshida K, Okuno Y, Sanada M, Xu Y, Doisaki S, Narita A, Kawashima N, Hama A, Takahashi Y, Yoshida N, Shiraishi Y, Chiba K, Tanaka H, Makishima H, Maciejewski J.P, Miyano S, Ogawa S, Kojima S.
Organizer
The 55th ASH Annual Meeting and Exposition.
Place of Presentation
New Orleans, USA
Related Report
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[Presentation] Aberrant DNA Methylation Is Associated With Poor Outcomes In Juvenile Myelomonocytic Leukemia.
Author(s)
Sakaguchi H, Muramatsu H, Wang X, Xu Y, Hibi Y, Kawashima N, Narita A, Doisaki S, Yoshida N, Hama A, Takahashi Y, Makishima H, Yamada K, Maciejewski JP, Kojima S.
Organizer
The 55th ASH Annual Meeting and Exposition.
Place of Presentation
New Orleans, USA
Related Report
