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Affiliation |
Faculty of Medicine School of Medicine Department of Internal Medicine, Hematology, Diabetes, and Endocrinology |
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Assistant Professor |
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External Link |
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KAMEDA Takuro
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Papers 【 display / non-display 】
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Integrated genetic and clinical prognostic factors for aggressive adult T-cell leukemia/lymphoma. Reviewed
Kameda T, Kataoka K, Kamiunten A, Hidaka M, Miyoshi H, Nakano N, Nosaka K, Yoshimitsu M, Yasunaga JI, Kogure Y, Shide K, Miyahara M, Sakamoto T, Akizuki K, Hidaka T, Kubuki Y, Koya J, Kawano N, Yamashita K, Kawano H, Toyama T, Maeda K, Marutsuka K, Imaizumi Y, Kato K, Sugio T, Tokunaga M, Tashiro Y, Takaori-Kondo A, Miyazaki Y, Akashi K, Ishitsuka K, Matsuoka M, Ohshima K, Watanabe T, Kitanaka A, Utsunomiya A, Ogawa S, Shimoda K
Haematologica 2023.2
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)
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Kameda T., Shide K., Kamiunten A., Kogure Y., Morishita D., Koya J., Tahira Y., Akizuki K., Yokomizo-Nakano T., Kubota S., Marutsuka K., Sekine M., Hidaka T., Kubuki Y., Kitai Y., Matsuda T., Yoda A., Ohshima T., Sugiyama M., Sashida G., Kataoka K., Ogawa S., Shimoda K.
Communications Biology 5 ( 1 ) 1309 2022.12
Authorship：Lead author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Communications Biology
Adult T-cell leukemia/lymphoma (ATL) is caused by human T-cell leukemia virus type 1 (HTLV-1). In addition to HTLV-1 bZIP factor (HBZ), a leukemogenic antisense transcript of HTLV-1, abnormalities of genes involved in TCR-NF-κB signaling, such as CARD11, are detected in about 90% of patients. Utilizing mice expressing CD4+ T cell-specific CARD11(E626K) and/or CD4+ T cell-specific HBZ, namely CARD11(E626K)CD4-Cre mice, HBZ transgenic (Tg) mice, and CARD11(E626K)CD4-Cre;HBZ Tg double transgenic mice, we clarify these genes’ pathogenetic effects. CARD11(E626K)CD4-Cre and HBZ Tg mice exhibit lymphocytic invasion to many organs, including the lungs, and double transgenic mice develop lymphoproliferative disease and increase CD4+ T cells in vivo. CARD11(E626K) and HBZ cooperatively activate the non-canonical NF-κB pathway, IRF4 targets, BATF3/IRF4/HBZ transcriptional network, MYC targets, and E2F targets. Most KEGG and HALLMARK gene sets enriched in acute-type ATL are also enriched in double transgenic mice, indicating that these genes cooperatively contribute to ATL development.
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Whole-genome landscape of adult T-cell leukemia/lymphoma Reviewed
Kogure Y., Kameda T., Koya J., Yoshimitsu M., Nosaka K., Yasunaga J.i., Imaizumi Y., Watanabe M., Saito Y., Ito Y., McClure M.B., Tabata M., Shingaki S., Yoshifuji K., Chiba K., Okada A., Kakiuchi N., Nannya Y., Kamiunten A., Tahira Y., Akizuki K., Sekine M., Shide K., Hidaka T., Kubuki Y., Kitanaka A., Hidaka M., Nakano N., Utsunomiya A., Sica R.A., Acuna-Villaorduna A., Janakiram M., Shah U., Ramos J.C., Shibata T., Takeuchi K., Takaori-Kondo A., Miyazaki Y., Matsuoka M., Ishitsuka K., Shiraishi Y., Miyano S., Ogawa S., Ye B.H., Shimoda K., Kataoka K.
Blood 139 ( 7 ) 967 - 982 2022.2
Authorship：Lead author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Blood
Adult T-cell leukemia/lymphoma (ATL) is an aggressive neoplasm immunophenotypically resembling regulatory T cells, associated with human T-cell leukemia virus type-1. Here, we performed whole-genome sequencing (WGS) of 150 ATL cases to reveal the overarching landscape of genetic alterations in ATL. We discovered frequent (33%) loss-of-function alterations preferentially targeting the CIC long isoform, which were overlooked by previous exome-centric studies of various cancer types. Long but not short isoform–specific inactivation of Cic selectively increased CD4+CD25+Foxp3+ T cells in vivo. We also found recurrent (13%) 3′-truncations of REL, which induce transcriptional upregulation and generate gain-of-function proteins. More importantly, REL truncations are also common in diffuse large B-cell lymphoma, especially in germinal center B-cell–like subtype (12%). In the non-coding genome, we identified recurrent mutations in regulatory elements, particularly splice sites, of several driver genes. In addition, we characterized the different mutational processes operative in clustered hypermutation sites within and outside immunoglobulin/T-cell receptor genes and identified the mutational enrichment at the binding sites of host and viral transcription factors, suggesting their activities in ATL. By combining the analyses for coding and noncoding mutations, structural variations, and copy number alterations, we discovered 56 recurrently altered driver genes, including 11 novel ones. Finally, ATL cases were classified into 2 molecular groups with distinct clinical and genetic characteristics based on the driver alteration profile. Our findings not only help to improve diagnostic and therapeutic strategies in ATL, but also provide insights into T-cell biology and have implications for genome-wide cancer driver discovery.
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Single-Cell Analysis of the Multicellular Ecosystem in Viral Carcinogenesis by HTLV-1. Reviewed
Koya J, Saito Y, Kameda T, Kogure Y, Yuasa M, Nagasaki J, McClure MB, Shingaki S, Tabata M, Tahira Y, Akizuki K, Kamiunten A, Sekine M, Shide K, Kubuki Y, Hidaka T, Kitanaka A, Nakano N, Utsunomiya A, Togashi Y, Ogawa S, Shimoda K, Kataoka K
Blood cancer discovery 2 ( 5 ) 450 - 467 2021.9
Language：English Publishing type：Research paper (scientific journal)
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Oncogenic isoform switch of tumor suppressor BCL11B in adult T-cell leukemia/lymphoma Reviewed
Permatasari H.K., Nakahata S., Ichikawa T., Fauzi Y.R., Kiyonari H., Shide K., Kameda T., Shimoda K., Ono M., Taki T., Taniwaki M., Futakuchi M., Morishita K.
Experimental Hematology 111 41 - 49 2022.7
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Experimental Hematology
B-Cell leukemia/lymphoma 11B (BCL11B) is a transcription factor important for T-cell development and acts as a tumor suppressor gene in T-cell acute lymphoblastic leukemia. Here, we identified BCL11B as a candidate leukemia-associated gene in human T-cell leukemia virus type 1 (HTLV-1)-induced adult T-cell leukemia/lymphoma (ATLL). Interestingly, the short form lacking exon 3 (BCL11B/S) protein was more highly expressed than the full-length BCL11B (BCL11B/L) in leukemic cells from most of the ATLL patients, although expression ratios of BCL11B/L to BCL11B/S were almost equal in control CD4+ T cells. BCL11B/S and BCL11B/L exhibited distinct subcellular localization and differential effects on cellular growth; BCL11B/L expression exhibited nuclear localization and inhibited cell growth in ATLL cells, whereas BCL11B/S exhibited nucleocytoplasmic distribution and accelerated cell growth. Furthermore, BCL11B/S expression accelerated the development of T-cell leukemia/lymphomas in transgenic mice carrying HTLV-1/HBZ, a critical viral factor in leukemogenesis, whereas these phenotypes did not occur in the double transgenic mice carrying BCL11B/L and HTLV-1/HBZ. In HTLV-1-infected T-cell lines, BCL11B expression is downregulated by HTLV-1/Tax, a viral factor necessary at the early stage of leukemogenesis. These results suggest that downregulation of BCL11B/L expression and upregulation of BCL11B/S may contribute to the development and progression of ATLL.
Books 【 display / non-display 】
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実践! IBD 診療
山本章二朗， 三池忠，安倍弘生，下田和哉（ Role： Joint author , 198-199）
医学出版 2014.5
Language：Japanese Book type：Scholarly book
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実践! IBD 診療
山本章二朗， 三池忠，安倍弘生，下田和哉（ Role： Joint author , 198-199）
医学出版 2014.5
Language：Japanese Book type：Scholarly book
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実践! IBD 診療
山本章二朗， 三池忠，安倍弘生，下田和哉（ Role： Joint author , 198-199）
医学出版 2014.5
Language：Japanese Book type：Scholarly book
Grant-in-Aid for Scientific Research 【 display / non-display 】
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ATL発症マウスモデルの作成と腫瘍生存シグナルの多様性を考慮した精密医療の確立
Grant number：23K07840 2023.04 - 2026.03
独立行政法人日本学術振興会 科学研究費基金 基盤研究(C)
Authorship：Principal investigator
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遺伝子改変マウスを用いたHTLV-1関連疾患の病態解明および新規治療法探索
Grant number：17K09931 2017.04 - 2020.03
科学研究費補助金 基盤研究(C)
Authorship：Principal investigator
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骨髄増殖性腫瘍における重複遺伝子異常の意義及び急性転化メカニズムの解明
Grant number：15K19554 2015.04 - 2017.03
科学研究費補助金 若手研究(B)
Authorship：Principal investigator