Development of epigenetic therapies for CNS leukemias
| Project/Area Number |
17K09938
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Jichi Medical University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 分子標的療法 / LSD1阻害剤 / 急性Tリンパ性白血病 / 中枢神経白血病 / エピジェネティクス / 急性リンパ性白血病 / 癌 / 血液腫瘍学 / T-ALL |
|---|
| Outline of Final Research Achievements |
Treatment outcome of T-cell acute lymphoblastic leukemia (T-ALL) is still worse than that of other hematologic malignancies.Despite the fundamental role of lysine-specific demethylase 1 (LSD1) in T-cell leukemogenesis, conventional LSD1 inhibitors, such as tranylcypromine (TCP), were shown to be ineffective for T-ALL cells in several preclinical studies. We therefore modified TCP to develop novel LSD1 inhibitors with higher activity and specificity for T-ALL. One of the newly developed inhibitors, S2157, showed robust cytotoxicity against TCP-resistant T-ALL cells both in vitro and in xenotransplanted mice. Notably, S2157 could eradicate CNS leukemia because of its ability to efficiently pass through the blood-brain barrier. This brain-permeable LSD1 inhibitor is promising as a novel therapeutic agent for T-ALL with CNS involvement.
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| Academic Significance and Societal Importance of the Research Achievements |
新規LSD1阻害剤S2157は、T-ALLに対して臨床応用可能なレベルの力価を有し、今まで治療が困難とされてきたCNS病変に対しても有効である可能性が示された。現在、T-ALLに対する分子標的薬として臨床応用されているものはなく、LSD1阻害剤はその第１号として既存の治療戦略への組み込みが期待される。
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Report
(4 results)
Research Products
(12 results)
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[Journal Article] Soluble SLAMF7 Promotes the Growth of Myeloma Cells via Homophilic Interaction with Surface SLAMF7.2020
Author(s)
Kikuchi J, Hori M, Iha H, Toyama-Sorimachi N, Hagiwara S, Kuroda Y, Koyama D, Izumi T, Yasui H, Suzuki A, Furukawa Y.
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Journal Title
Leukemia.
Volume: 34
Issue: 1
Pages: 180-195
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Eradication of central nervous system leukemia of T-cell origin with a brain-permeable LSD1 inhibitor.2019
Author(s)
Saito S, Kikuchi J, Koyama D, Sato S, Koyama H, Osada N, Kuroda Y, Akahane K, Inukai T, Umehara T, Furukawa Y.
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Journal Title
Clin Cancer Res
Volume: 25
Issue: 5
Pages: 1601-1611
DOI
Related Report
Peer Reviewed
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