| Project/Area Number |
18K19960
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| Research Category |
Fund for the Promotion of Joint International Research (Home-Returning Researcher Development Research)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Biological Sciences
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| Research Institution | Nagoya City University |
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Principal Investigator |
Sanda Takaomi 名古屋市立大学, 医薬学総合研究院(医学), 准教授 (00792475)
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| Co-Investigator(Kenkyū-buntansha) |
飯田 真介 名古屋市立大学, 医薬学総合研究院(医学), 教授 (50295614)
鈴木 智貴 名古屋市立大学, 医薬学総合研究院(医学), 助教 (80834001)
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| Project Period (FY) |
2020-04-01 – 2025-03-31
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| Project Status |
Completed (Fiscal Year 2024)
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| Budget Amount *help |
¥61,620,000 (Direct Cost: ¥47,400,000、Indirect Cost: ¥14,220,000)
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| Keywords | Hematological malignancy / Enhancer / Transcription factor / Oncogene / T-ALL / ATL / エンハンサー解析 / クロマチン解析 / 遺伝子発現解析 / T細胞性急性リンパ性白血病 / 造血器腫瘍 / エンハンサー / クロマチン / 遺伝子発現 / ゲノム / ゲノム解析 / 転写因子 / T細胞性白血病 |
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| Outline of Final Research Achievements |
In this project, we aimed to identify the enhancers that are abnormally activated in hematological malignancies as well as to clarify the roles of oncogenic transcription factors. Our goal was to understand molecular pathogenesis and to develop novel therapeutics via these approaches. More specifically, in T-cell acute lymphoblastic leukemia (T-ALL), we demonstrated that the oncogenic transcription factor TAL1 aberrantly induces downstream targets that are normally not expressed in developing T-cells and also blocks T-cell differentiation, by which it contributes to T-cell leukemogenesis. Moreover, the transcription factor MYB plays TAL1-dependent and -independent roles in T-ALL. Additionally, we demonstrated that in adult T-cell leukemia (ATL), TP73 is expressed under a super-enhancer and its expression and exon deletion contributes to ATL cell proliferation.
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| Academic Significance and Societal Importance of the Research Achievements |
本課題では、各種造血器腫瘍において癌化に関わる遺伝子とその調節領域の同定、並びに遺伝子発現プログラムの解明を通して、それぞれの分子病態の理解を深めた。また、本課題で用いたタンパク分解システムや薬剤の効果を通して、癌遺伝子の治療標的としての意義を明らかにした。さらには、新たに着目した遺伝子・エンハンサーの臨床的検討により、その予後予測マーカーとしての意義を明らかにした。
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