Leukemic development through chromosomal translocation with super-enhancer exchange
| Project/Area Number |
18K16090
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 54010:Hematology and medical oncology-related
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| Research Institution | Kumamoto University |
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Principal Investigator |
Kubota Sho 熊本大学, 国際先端医学研究機構, 特定事業研究員 (70747831)
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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 |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | BPDCN / エンハンサー / エピジェネティクス / 白血病 / 染色体転座 / スーパーエンハンサー / エピゲノム / RUNX2 / MYC / Super-enhancer / enhancer hijacking |
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| Outline of Final Research Achievements |
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive acute leukemia, which appears to be originated from the precursor of plasmacytoid dendritic cells (pDCs). Chromosomal translocation (6;8)(p21;q24) is often seen in BPDCN patients. RUNX2, located on chromosome 6p21, has been shown to regulate the differentiation of pDCs. We found that expression of RUNX2 and C-MYC, an potent oncogene, were significantly up-regulated in BPDCN bone marrow cells in patients as well as a cell line, CAL-1, harboring t(6;8)(p21;q24). Given that RUNX2 appeared to be critical for the development of BPDCN, we explored the mechanism of pathogenesis of BPDCN driven by t(6;8).
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| Academic Significance and Societal Importance of the Research Achievements |
がん遺伝子MYCの活性化機構として、従来、MYC遺伝子増幅や染色体転座によるプロモーターの置換が知られていた。また、組織特異的なエンハンサーが異常に活性化する膵臓がん、大腸がんや急性リンパ性白血病の場合もある。本研究では、染色体相互転座によって、c-MYCエンハンサーがRUNX2を、RUNX2スーパーエンハンサーがc-MYC発現を異常に活性化する機構を明らかにした。こうした染色体転座によって交換・活性化されたがん特異的エンハンサーによるBPDCN発症機構の解明は、MYCの新規活性化機構だけに限らず、新たながん発症メカニズムの視点を与えた独創的な研究である。
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Report
(4 results)
Research Products
(8 results)
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[Journal Article] Lineage-specific RUNX2 super-enhancer activates MYC via a chromosomal translocation and promotes the development of blastic plasmacytoid dendritic cell neoplasm2019
Author(s)
Kubota S, Tokunaga K, Umezu T, Yokomizo-Nakano T, Oshima M, Tan KT, Yang H, Kanai A. Iwanaga E, Asou N, Maeda T, Nakagata N. Ito T, Iwama A. Ohyashiki K, Osato M, Sashida G.
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Journal Title
Nat Commun
Volume: 10
Issue: 1
Pages: 1653-1653
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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