Development of novel therapy for MLL-rearranged leukemia
| Project/Area Number |
16H05337
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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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| Research Field |
Hematology
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| Research Institution | National Cancer Center Japan (2017-2018)
Kyoto University (2016) |
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Principal Investigator |
Yokoyama Akihiko 国立研究開発法人国立がん研究センター, 研究所, ユニット長 (10506710)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2018: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
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| Keywords | 白血病 / 分子標的薬 / 転写 / クロマチン / エピジェネティクス / MLL / 遺伝子発現 / MENIN / DOT1L / がん / がん幹細胞 / 治療法 / 転写制御 / 分子病態 |
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| Outline of Final Research Achievements |
Leukemias carrying mutations of the MLL gene are frequently found in infants and often associated with poor prognosis. We investigated the molecular mechanisms of MLL-associated leukemia and proposed a novel therapeutic approach based on our findings.
MLL is a protein responsible for gene regulation. We found that MLL mutant proteins function as a hyper-active gene regulator dependently on two proteins, namely, AF4 and DOT1L. We showed experimentally that simultaneous inhibition of these two proteins by molecularly-targeted drugs exerted strong anti-tumor effects in mouse disease models.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、がん治療法の開発はがん細胞が依存している特定のタンパク質を標的とした分子標的療法の開発に向かっている。しかし、開発中の化合物は単剤で十分な治療効果を得る事ができない場合も多い。現状の臨床現場では、まだほとんどの場合で古くから使われている抗がん剤に依存した治療が行われている。本研究成果は、がん化の分子メカニズムの一端を明らかにすると共に、得られた知見に基づいて新しい治療法を提案した点で学術的、社会的意義がある。
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Report
(4 results)
Research Products
(15 results)
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[Journal Article] Mutant ASXL1 cooperates with BAP1 to promote myeloid leukaemogenesis2018
Author(s)
Asada S, Goyama S, Inoue D, Shikata S, Takeda R, Fukushima T, Yonezawa T, Fujino T, Hayashi Y, Kawabata KC, Fukuyama T, Tanaka Y, Yokoyama A, Yamazaki S, Kozuka-Hata H, Oyama M, Kojima S, Kawazu M, Mano H, Kitamura T
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Journal Title
Nat Commun
Volume: 9
Issue: 1
Pages: 2733-2733
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] A novel ASXL1?OGT axis plays roles in H3K4 methylation and tumor suppression in myeloid malignancies2018
Author(s)
Inoue D, Fujino T, Sheridan P, Zhang YZ, Nagase R, Horikawa S, Li Z, Matsui H, Kanai A, Saika M, Yamaguchi R, Kozuka-Hata H, Kawabata KC, Yokoyama A, Goyama S, Inaba T, Imoto S, Miyano S, Xu M, Yang FC, Oyama M, Kitamura T.
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Journal Title
Leukemia
Volume: 印刷中
Issue: 6
Pages: 1327-1337
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] MLL2, Not MLL1, Plays a Major Role in Sustaining MLL-Rearranged Acute Myeloid Leukemia.2017
Author(s)
Yufei Chen, Konstantinos Anastassiadis, Andrea Kranz, A. Francis Stewart, Kathrin Arndt, Claudia Waskow, Akihiko Yokoyama, Kenneth Jones, Tobias Neff, Yoo Lee, Patricia Ernst
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Journal Title
Cancer Cell
Volume: 31
Issue: 6
Pages: 755-770
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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