@misc{oai:niigata-u.repo.nii.ac.jp:00006001, author = {Tanaka, Tomoyuki}, month = {Mar}, note = {Recurrent inactivating mutations have been identified in various hematological malignancies in the X-linked BCOR gene encoding BCL6 corepressor (BCOR). However, its tumor suppressor function remains largely uncharacterized. We herein generated mice missing Bcor exon 4, expressing a variant BCOR lacking the BCL6-binding domain. While the deletion of exon 4 in male mice (Bcor^ <ΔE4/y>) compromised the repopulating capacity of hematopoietic stem cells, Bcor^<ΔE4/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 Bcor^<ΔE4/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 Bcor^<ΔE4/y> thymocytes. Our results provide the first evidence of a tumor suppressor role for BCOR in the pathogenesis of T lymphocyte malignancies., 学位の種類: 博士(医学). 報告番号: 甲第4403号. 学位記番号: 新大院博(医)甲第802号. 学位授与年月日: 平成30年3月23日, Journal of Experimental Medicine. 2017. 214(10), 2901-2913., 新大院博(医)甲第802号}, title = {Internal deletion of BCOR reveals a tumor suppressor function for BCOR in T lymphocyte malignancies}, year = {2018} }