Development of a novel therapeutic strategy targeting MYC for leukemia with monosomy 7
Project/Area Number |
21K16241
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 54010:Hematology and medical oncology-related
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Research Institution | The University of Tokyo |
Principal Investigator |
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Project Period (FY) |
2021-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2022: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2021: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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Keywords | モノソミー7 / 合成致死 / MYC / エピゲノム / BRD4 |
Outline of Research at the Start |
7番染色体のモノソミー(モノソミー7)を伴う白血病は化学療法に抵抗性で予後不良であり、分子病態に基づいた特異的な治療法の開発が切望されている。我々は、ヒストン修飾遺伝子を対象とした独自のスクリーニングを行い、モノソミー7白血病の生存に必須である遺伝子を複数同定した。興味深いことに、これら遺伝子はいずれもMYCを標的遺伝子としていることが一連の解析から明らかとなった。これらの知見に基づいて、本研究ではMYC遺伝子に着目したモノソミー7に対する新しい治療戦略の開発・応用を目指す。
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Outline of Final Research Achievements |
The aim of this study is to develop MYC-targeted therapies for leukemias with monosomy of chromosome 7 (monosomy 7). Our group identified several target genes in a therapeutic target screen based on the concept of synthetic lethality, suggesting that they may exert their effects by downregulating MYC. Using leukemia cell lines and patient samples, we confirmed that MYC inhibitory therapy inhibited the growth of monosomy 7 leukemia cells. In addition, we found that MYC inhibition contribute to a lower tumor progression and mouse survival in an immunodeficient mouse model. MYC is required for survival. MYC is an essential gene for cell function, but its expression level was suppressed to a lower level in monosomy 7 leukemia, which may induce the vulnerability to MYC inhibitory therapy.
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Academic Significance and Societal Importance of the Research Achievements |
本研究では、難治性であるモノソミー7を伴う白血病の新しい脆弱性を明らかにした。加えて、本研究は、染色体欠失という事象に対して、新しい治療標的探索アプローチを提示する可能性がある。本研究が発展し、難治性白血病に対する新しい治療法の開発及び治療成績向上が期待される。
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Report
(3 results)
Research Products
(23 results)
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[Journal Article] Comparison of transplant outcomes between haploidentical transplantation and single cord blood transplantation in non‐remission acute myeloid leukaemia: A nationwide retrospective study2023
Author(s)
K Matsuda , T Konuma , K Fuse , M Masuko , K Kawamura , M Hirayama , N Uchida , K Ikegame , A Wake , T Eto , N Doki , S Miyakoshi , M Tanaka , S Takahashi , M Onizuka , K Kato , T Kimura , T Ichinohe , N Takayama , H Kobayashi , H Nakamae , Y Atsuta , J Kanda , M Yanada
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Journal Title
British Journal of Haematology
Volume: 201
Issue: 1
Pages: 106-113
DOI
Related Report
Peer Reviewed / Open Access
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[Book] 血液内科2022
Author(s)
松田健佑、牧宏彰、黒川峰夫
Total Pages
5
Publisher
科学評論社
Related Report