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Faculty of Medicine School of Medicine Department of Internal Medicine, Hematology, Diabetes, and Endocrinology |
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Assistant Professor |
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Related SDGs |
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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 Takuro, Kataoka Keisuke, Kamiunten Ayako, Hidaka Michihiro, Miyoshi Hiroaki, Nakano Nobuaki, Nosaka Kisato, Yoshimitsu Makoto, Yasunaga Jun-Ichirou, Kogure Yasunori, Shide Kotaro, Miyahara Masaharu, Sakamoto Takashi, Akizuki Keiichi, Hidaka Tomonori, Kubuki Yoko, Koya Junji, Kawano Noriaki, Yamashita Kiyoshi, Kawano Hiroshi, Toyama Takanori, Maeda Kouichi, Marutsuka Kosuke, Imaizumi Yoshitaka, Kato Koji, Sugio Takeshi, Tokunaga Masahito, Tashiro Yukie, Takaori-Kondo Akifumi, Miyazaki Yasushi, Akashi Koichi, Ishitsuka Kenji, Matsuoka Masao, Ohshima Koichi, Watanabe Toshiki, Kitanaka Akira, Utsunomiya Atae, Ogawa Seishi, Shimoda Kazuya
Haematologica 108 ( 8 ) 2178 - 2191 2023.2
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)
The prognosis of aggressive adult T-cell leukemia/lymphoma (ATL) is poor, and allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is a curative treatment. To identify favorable prognostic patients after intensive chemotherapy, and who therefore might not require upfront allo-HSCT, we aimed to improve risk stratification of aggressive ATL patients aged <70 years. The clinical risk factors and genetic mutations were incorporated into risk modeling for overall survival (OS). We generated the m7-ATLPI, a clinicogenetic risk model for OS, that included the ATL prognostic index (PI) (ATL-PI) risk category, and non-silent mutations in seven genes, namely TP53, IRF4, RHOA, PRKCB, CARD11, CCR7, and GATA3. In the training cohort of 99 patients, the m7-ATLPI identified a low-, intermediate-, and high-risk group with 2-year OS of 100%, 43%, and 19%, respectively (hazard ratio [HR] 5.46, p < 0.0001). The m7-ATLPI achieved superior risk stratification compared to the current ATL-PI (C-index 0.92 vs. 0.85, respectively). In the validation cohort of 84 patients, the m7-ATLPI defined low-, intermediate-, and high-risk groups with a 2-year OS of 81%, 30%, and 0%, respectively (HR 2.33, p = 0.0094), and the model again outperformed the ATL-PI (C-index 0.72 vs. 0.70, respectively). The simplified m7-ATLPI, which is easier to use in clinical practice, achieved superior risk stratification compared to the ATL-PI, as did the original m7-ATLPI; the simplified version was calculated by summing the following: high-risk ATL-PI category (+10), low-risk ATL-PI category (−4), and non-silent mutations in TP53 (+4), IRF4 (+3), RHOA (+1), PRKCB (+1), CARD11 (+0.5), CCR7 (−2), and GATA3 (−3).
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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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Impaired humoral immunity following COVID-19 vaccination in HTLV-1 carriers Reviewed
Kameda T., Utsunomiya A., Otsuka N., Kubuki Y., Uchida T., Shide K., Kamiunten A., Nakano N., Tokunaga M., Miyazono T., Ito Y., Yonekura K., Kawakita T., Akizuki K., Tahira Y., Karasawa M., Hidaka T., Konagata A., Taniguchi N., Nagatomo Y., Kogo F., Shimizu K., Ueno H., Ishizaki J., Takahashi N., Ikei Y., Hidaka M., Yamaguchi H., Shimoda K.
BMC Infectious Diseases 24 ( 1 ) 96 2024.12
Language：English Publishing type：Research paper (scientific journal) Publisher：BMC Infectious Diseases
Background: Whether human T-lymphotropic virus type 1 (HTLV-1) carriers can develop sufficient humoral immunity after coronavirus disease 2019 (COVID-19) vaccination is unknown. Methods: To investigate humoral immunity after COVID-19 vaccination in HTLV-1 carriers, a multicenter, prospective observational cohort study was conducted at five institutions in southwestern Japan, an endemic area for HTLV-1. HTLV-1 carriers and HTLV-1-negative controls were enrolled for this study from January to December 2022. During this period, the third dose of the COVID-19 vaccine was actively administered. HTLV-1 carriers were enrolled during outpatient visits, while HTLV-1-negative controls included health care workers and patients treated by participating institutions for diabetes, hypertension, or dyslipidemia. The main outcome was the effect of HTLV-1 infection on the plasma anti-COVID-19 spike IgG (IgG-S) titers after the third dose, assessed by multivariate linear regression with other clinical factors. Results: We analyzed 181 cases (90 HTLV-1 carriers, 91 HTLV-1-negative controls) after receiving the third dose. HTLV-1 carriers were older (median age 67.0 vs. 45.0 years, p < 0.001) and more frequently had diabetes, hypertension, or dyslipidemia than did HTLV-1-negative controls (60.0% vs. 27.5%, p < 0.001). After the third dose, the IgG-S titers decreased over time in both carriers and controls. Multivariate linear regression in the entire cohort showed that time since the third dose, age, and HTLV-1 infection negatively influenced IgG-S titers. After adjusting for confounders such as age, or presence of diabetes, hypertension, or dyslipidemia between carriers and controls using the overlap weighting propensity score method, and performing weighted regression analysis in the entire cohort, both time since the third dose and HTLV-1 infection negatively influenced IgG-S titers. Conclusions: The humoral immunity after the third vaccination dose is impaired in HTLV-1 carriers; thus, customized vaccination schedules may be necessary for them.
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
MISC 【 display / non-display 】
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Shide K., Takenaka K., Kitanaka A., Numata A., Kameda T., Yamauchi T., Inagaki A., Mizuno S., Takami A., Ito S., Hagihara M., Usuki K., Maekawa T., Sunami K., Ueda Y., Tsutsui M., Ando M., Komatsu N., Ozawa K., Kurokawa M., Arai S., Mitani K., Akashi K., Shimoda K.
Blood Cancer Journal 13 ( 1 ) 110 2023.12
Language：English Publishing type：Rapid communication, short report, research note, etc. (scientific journal) Publisher：Blood Cancer Journal
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