Mechanisms for effectiveness of hypo-methylating agent for TP53-mutated MDS
| Project/Area Number |
18H02836
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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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| Review Section |
Basic Section 54010:Hematology and medical oncology-related
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2019: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2018: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
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| Keywords | 骨髄異形成症候群 / 脱メチル化剤 / 有効性マーカー / TP53 / MDS / アザシチジン / 有効性メカニズム / ＴＰ５３ |
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| Outline of Final Research Achievements |
TP53 mutated myelodysplastic syndromes are extremely refractory and there is still no effective treatment. Recently, the demethylating agent, azacitidine, has been reported to have a high remission rate, but many cases eventually relapse. In this study, we showed that TP53 mutated MDS cases have very different biological features and clinical significance depending on allele status (whether one or both of the two human genes are altered), and should be considered as distinct conditions. Furthermore, we examined the size of the mutant cell population (clone) before and after azacitidine treatment, and showed that it is important to examine the type of mutation and its size after treatment in order to understand the pathogenesis and predict prognosis.
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| Academic Significance and Societal Importance of the Research Achievements |
TP53変異陽性骨髄異形成症候群をアレルの状態によって区別することで、予後予測が最適化され、移植適応などの治療方針も変化する。アザシチジン治療前後の変異パターンとその大きさを計測することで、病態の把握が正確になり、長期予後予測の精度が高まる。特に治療後クローン性造血がみられるという知見は、治療後残存クローンの正しい解釈に重要である。
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Report
(4 results)
Research Products
(13 results)
