亀田 拓郎 (カメダ タクロウ)

KAMEDA Takuro

写真a

所属

医学部 医学科 内科学講座血液・糖尿病・内分泌内科学分野

職名

助教

外部リンク

 

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  • CARD11 mutation and HBZ expression induce lymphoproliferative disease and adult T-cell leukemia/lymphoma 査読あり

    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年12月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元: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.

    DOI: 10.1038/s42003-022-04284-x

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    PubMed

  • Oncogenic isoform switch of tumor suppressor BCL11B in adult T-cell leukemia/lymphoma 査読あり

    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年7月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元: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.

    DOI: 10.1016/j.exphem.2022.04.004

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    PubMed

  • Prognosis of Indolent Adult T-Cell Leukemia/Lymphoma 査読あり

    Kameda T., Shide K., Tahira Y., Sekine M., Sato S., Ishizaki J., Takeuchi M., Akizuki K., Kamiunten A., Shimoda H., Toyama T., Maeda K., Yamashita K., Kawano N., Kawano H., Hidaka T., Yamaguchi H., Kubuki Y., Kitanaka A., Matsuoka H., Shimoda K.

    Viruses   14 ( 4 )   2022年4月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Viruses  

    A retrospective chart survey of the clinical features of indolent adult T-cell leukemia/lymphoma (ATL) was conducted in the Miyazaki Prefecture, Japan. This study enrolled 24 smoldering-type ATLs, 10 favorable chronic-type ATLs, and 20 unfavorable chronic-type ATLs diagnosed between 2010 and 2018. Among them, 4, 3, and 10 progressed to acute-type ATLs during their clinical course. The median survival time (MST) in smoldering-type ATL and favorable chronic-type ATL was not reached, and their 4-year overall survival (OS) was 73% and 79%, respectively. Compared with this, the prognosis of unfavorable chronic-type ATL was poor. Its MST was 3.32 years, and the 4-year OS was 46% (p = 0.0095). In addition to the three features that determine the unfavorable characteristics of chronic-type ATL, namely, increased lactate dehydrogenase, increased blood urea nitrogen, and decreased albumin, the high-risk category by the indolent ATL-Prognostic Index, which was defined by an increment of soluble interleukin-2 receptor (sIL2-R) of >6000 U/mL, could explain the poor prognosis in indolent ATL patients. The level of sIL-2R might be an indicator of the initiation of therapy for indolent ATL.

    DOI: 10.3390/v14040710

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    PubMed

  • Whole-genome landscape of adult T-cell leukemia/lymphoma 査読あり

    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年2月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元: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.

    DOI: 10.1182/blood.2021013568

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    PubMed

  • Single-Cell Analysis of the Multicellular Ecosystem in Viral Carcinogenesis by HTLV-1. 査読あり

    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年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1158/2643-3230.BCD-21-0044

    PubMed

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書籍等出版物 【 表示 / 非表示

  • 実践! IBD 診療

    山本章二朗, 三池忠,安倍弘生,下田和哉( 担当: 共著 ,  範囲: 198-199)

    医学出版  2014年5月 

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    記述言語:日本語 著書種別:学術書

  • 実践! IBD 診療

    山本章二朗, 三池忠,安倍弘生,下田和哉( 担当: 共著 ,  範囲: 198-199)

    医学出版  2014年5月 

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    記述言語:日本語 著書種別:学術書

  • 実践! IBD 診療

    山本章二朗, 三池忠,安倍弘生,下田和哉( 担当: 共著 ,  範囲: 198-199)

    医学出版  2014年5月 

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    記述言語:日本語 著書種別:学術書

科研費(文科省・学振・厚労省)獲得実績 【 表示 / 非表示

  • 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

    2017年04月 - 2020年03月

    科学研究費補助金  基盤研究(C)

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    担当区分:研究代表者 

  • 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

    2015年04月 - 2017年03月

    科学研究費補助金  若手研究(B)

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    担当区分:研究代表者