Tumor suppressor role of BCOR in hematopoiesis
Project/Area Number |
16K15498
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Hematology
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Research Institution | Chiba University |
Principal Investigator |
Iwama Atsushi 千葉大学, 大学院医学研究院, 教授 (70244126)
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Project Period (FY) |
2016-04-01 – 2018-03-31
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Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Keywords | BCOR / がん抑制遺伝子 / 造血腫瘍 / Bcor / 急性リンパ芽球せい白血病 / 急性Tリンパ芽球性白血病 / ポリコーム群複合体 / 造血器腫瘍 |
Outline of Final Research Achievements |
Recurrent inactivating mutations have been identified in various hematological malignancies in the X-linked BCOR gene encoding BCL6 corepressor (BCOR). We herein generated mice missing Bcor exon 4, expressing a variant BCOR lacking the BCL6-binding domain (BcorΔE4/y). BcorΔE4/y thymocytes had augmented proliferative capacity in culture and showed a strong propensity to induce acute T-cell lymphoblastic leukemia (T-ALL) mostly in a Notch-dependent manner. Myc, one of the critical NOTCH1 targets in T-ALL, was highly upregulated in BcorΔE4/y T-ALL cells. ChIP-seq analysis revealed that BCOR was recruited to the Myc promoter and restrained its activation in thymocytes. BCOR also targeted other NOTCH1 targets and potentially antagonized their transcriptional activation. Bcl6-deficient thymocytes behaved in a similar manner to BcorΔE4/y thymocytes. Our results provide the first evidence of a tumor suppressor role for BCOR in the pathogenesis of T lymphocyte malignancies.
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Report
(3 results)
Research Products
(10 results)
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[Journal Article] Recurrent SPI1 (PU.1) fusions in high-risk pediatric T cell acute lymphoblastic leukemia.2017
Author(s)
Seki M, Kimura S, Isobe T, Yoshida K, (13 authors), Masuda K, Kawamoto H, Ohki K, Kato M, Arakawa Y, Koh K, Hanada R, Moritake H, Akiyama M, Kobayashi R, Deguchi T, Hashii Y, Imamura T, Sato A, Kiyokawa N, Oka A, Hayashi Y, Takagi M, Manabe A, Ohara A, Horibe K, Sanada M, Iwama A, Mano H, Miyano S, Ogawa S, Takita J
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Journal Title
Nature Genetics
Volume: 49
Issue: 8
Pages: 1274-1281
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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