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1. Whole-genome landscape of adult T-cell leukemia/lymphoma

Author

Kogure, Yasunori, Kameda, Takuro, Koya, Junji, Yoshimitsu, Makoto, Nosaka, Kisato, Yasunaga, Jun-ichirou, Imaizumi, Yoshitaka, Watanabe, Mizuki, Saito, Yuki, Ito, Yuta, McClure, Marni B., Tabata, Mariko, Shingaki, Sumito, Yoshifuji, Kota, Chiba, Kenichi, Okada, Ai, Kakiuchi, Nobuyuki, Nannya, Yasuhito, Kamiunten, Ayako, Tahira, Yuki, Akizuki, Keiichi, Sekine, Masaaki, Shide, Kotaro, Hidaka, Tomonori, Kubuki, Yoko, Kitanaka, Akira, Hidaka, Michihiro, Nakano, Nobuaki, Utsunomiya, Atae, Sica, R. Alejandro, Acuna-Villaorduna, Ana, Janakiram, Murali, Shah, Urvi, Ramos, Juan Carlos, Shibata, Tatsuhiro, Takeuchi, Kengo, Takaori-Kondo, Akifumi, Miyazaki, Yasushi, Matsuoka, Masao, Ishitsuka, Kenji, Shiraishi, Yuichi, Miyano, Satoru, Ogawa, Seishi, Ye, B. Hilda, Shimoda, Kazuya, and Kataoka, Keisuke

Published
2022
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2. Prognostic relevance of integrated genetic profiling in adult T-cell leukemia/lymphoma

Author

Kataoka, Keisuke, Iwanaga, Masako, Yasunaga, Jun-ichirou, Nagata, Yasunobu, Kitanaka, Akira, Kameda, Takuro, Yoshimitsu, Makoto, Shiraishi, Yuichi, Sato-Otsubo, Aiko, Sanada, Masashi, Chiba, Kenichi, Tanaka, Hiroko, Ochi, Yotaro, Aoki, Kosuke, Suzuki, Hiromichi, Shiozawa, Yusuke, Yoshizato, Tetsuichi, Sato, Yusuke, Yoshida, Kenichi, Nosaka, Kisato, Hishizawa, Masakatsu, Itonaga, Hidehiro, Imaizumi, Yoshitaka, Munakata, Wataru, Shide, Kotaro, Kubuki, Yoko, Hidaka, Tomonori, Nakamaki, Tsuyoshi, Ishiyama, Ken, Miyawaki, Shuichi, Ishii, Ryohei, Nureki, Osamu, Tobinai, Kensei, Miyazaki, Yasushi, Takaori-Kondo, Akifumi, Shibata, Tatsuhiro, Miyano, Satoru, Ishitsuka, Kenji, Utsunomiya, Atae, Shimoda, Kazuya, Matsuoka, Masao, Watanabe, Toshiki, and Ogawa, Seishi

Published
2018
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3. Variegated RHOA mutations in adult T-cell leukemia/lymphoma

Author

Nagata, Yasunobu, Kontani, Kenji, Enami, Terukazu, Kataoka, Keisuke, Ishii, Ryohei, Totoki, Yasushi, Kataoka, Tatsuki R., Hirata, Masahiro, Aoki, Kazuhiro, Nakano, Kazumi, Kitanaka, Akira, Sakata-Yanagimoto, Mamiko, Egami, Sachiko, Shiraishi, Yuichi, Chiba, Kenichi, Tanaka, Hiroko, Shiozawa, Yusuke, Yoshizato, Tetsuichi, Suzuki, Hiromichi, Kon, Ayana, Yoshida, Kenichi, Sato, Yusuke, Sato-Otsubo, Aiko, Sanada, Masashi, Munakata, Wataru, Nakamura, Hiromi, Hama, Natsuko, Miyano, Satoru, Nureki, Osamu, Shibata, Tatsuhiro, Haga, Hironori, Shimoda, Kazuya, Katada, Toshiaki, Chiba, Shigeru, Watanabe, Toshiki, and Ogawa, Seishi

Published
2016
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4. Loss of TET2 has dual roles in murine myeloproliferative neoplasms: disease sustainer and disease accelerator

Author

Kameda, Takuro, Shide, Kotaro, Yamaji, Takumi, Kamiunten, Ayako, Sekine, Masaaki, Taniguchi, Yasuhiro, Hidaka, Tomonori, Kubuki, Yoko, Shimoda, Haruko, Marutsuka, Kousuke, Sashida, Goro, Aoyama, Kazumasa, Yoshimitsu, Makoto, Harada, Taku, Abe, Hiroo, Miike, Tadashi, Iwakiri, Hisayoshi, Tahara, Yoshihiro, Sueta, Mitsue, Yamamoto, Shojiro, Hasuike, Satoru, Nagata, Kenji, Iwama, Atsushi, Kitanaka, Akira, and Shimoda, Kazuya

Published
2015
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7. Physiological Expression of Calr Mutant Increases Cell Growth and Cytokine Independency in Human Cell Lines Expressing Mpl, and Develops Essential Thrombocythemia in Mice

Author

Shide, Kotaro, primary, Kameda, Takuro, additional, Sekine, Masaaki, additional, Kamiunten, Ayako, additional, Akizuki, Keiichi, additional, Tahira, Yuki, additional, Hidaka, Tomonori, additional, Kubuki, Yoko, additional, Honda, Arata, additional, Sawaguchi, Akira, additional, Kitanaka, Akira, additional, and Shimoda, Kazuya, additional

Published
2016
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8. Mogamulizumab for ATLL in Clinical Practice

Author

Sekine, Masaaki, primary, Takeuchi, Masaki, additional, Toyama, Takanori, additional, Maeda, Kouichi, additional, Sato, Seiichi, additional, Yamashita, Kiyoshi, additional, Ishizaki, Junzo, additional, Keiichi, Akizuki, additional, Kamiunten, Ayako, additional, Kameda, Takuro, additional, Shide, Kotaro, additional, Hidaka, Tomonori, additional, Kubuki, Yoko, additional, Kitanaka, Akira, additional, and Shimoda, Kazuya, additional

Published
2016
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9. Next-Generation Sequencing Reveal Proviral Genome and Transcriptome in Adult T-Cell Leukemia/Lymphoma

Author

Kataoka, Keisuke, primary, Nagata, Yasunobu, additional, Kitanaka, Akira, additional, Shiraishi, Yuichi, additional, Totoki, Yasushi, additional, Yasunaga, Jun-ichirou, additional, Chiba, Kenichi, additional, Sato-Otsubo, Aiko, additional, Sanada, Masashi, additional, Tanaka, Hiroko, additional, Shiozawa, Yusuke, additional, Yoshizato, Tetsuichi, additional, Yoshida, Kenichi, additional, Makishima, Hideki, additional, Hishizawa, Masakatsu, additional, Itonaga, Hidehiro, additional, Imaizumi, Yoshitaka, additional, Munakata, Wataru, additional, Hiromi, Nakamura, additional, Hama, Natsuko, additional, Shide, Kotaro, additional, Kubuki, Yoko, additional, Hidaka, Tomonori, additional, Kameda, Takuro, additional, Nakamaki, Tsuyoshi, additional, Tobinai, Kensei, additional, Miyazaki, Yasushi, additional, Takaori-Kondo, Akifumi, additional, Matsuoka, Masao, additional, Shibata, Tatsuhiro, additional, Miyano, Satoru, additional, Shimoda, Kazuya, additional, and Ogawa, Seishi, additional

Published
2015
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10. All-Trans Retinoic Acid and Interferon-Alpha Increase CD38 Expression on Adult T-Cell Leukemia Cells and Sensitize Them to T Cells Bearing Anti-CD38 Chimeric Antigen Receptors

Author

Mihara, Keichiro, primary, Yoshida, Tetsumi, additional, Ishida, Seiko, additional, Takei, Yoshifumi, additional, Kitanaka, Akira, additional, Shimoda, Kazuya, additional, Morishita, Kazuhiro, additional, Takihara, Yoshihiro, additional, and Ichinohe, Tatsuo, additional

Published
2015
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11. Prognostic Relevance of Integrated Genetic Profiling in Adult T-Cell Leukemia/Lymphoma

Author

Kataoka, Keisuke, primary, Nagata, Yasunobu, additional, Kitanaka, Akira, additional, Yasunaga, Jun-ichirou, additional, Iwanaga, Masako, additional, Shiraishi, Yuichi, additional, Chiba, Kenichi, additional, Sato-Otsubo, Aiko, additional, Sanada, Masashi, additional, Tanaka, Hiroko, additional, Suzuki, Hiromichi, additional, Sato, Yusuke, additional, Shiozawa, Yusuke, additional, Yoshizato, Tetsuichi, additional, Yoshida, Kenichi, additional, Makishima, Hideki, additional, Nosaka, Kisato, additional, Hishizawa, Masakatsu, additional, Itonaga, Hidehiro, additional, Imaizumi, Yoshitaka, additional, Munakata, Wataru, additional, Shide, Kotaro, additional, Kubuki, Yoko, additional, Hidaka, Tomonori, additional, Kameda, Takuro, additional, Nakamaki, Tsuyoshi, additional, Ishiyama, Ken, additional, Miyawaki, Shuichi, additional, Tobinai, Kensei, additional, Miyazaki, Yasushi, additional, Takaori-Kondo, Akifumi, additional, Shibata, Tatsuhiro, additional, Miyano, Satoru, additional, Matsuoka, Masao, additional, Shimoda, Kazuya, additional, Watanabe, Toshiki, additional, and Ogawa, Seishi, additional

Published
2015
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12. Frequent Activating Somatic Alterations in T-Cell Receptor / NF-κb Signaling in Adult T-Cell Leukemia/Lymphoma

Author

Kataoka, Keisuke, primary, Nagata, Yasunobu, additional, Kitanaka, Akira, additional, Shiraishi, Yuichi, additional, Yasunaga, Jun-ichirou, additional, Totoki, Yasushi, additional, Chiba, Kenichi, additional, Sato-Otsubo, Aiko, additional, Kotani, Shinichi, additional, Sanada, Masashi, additional, Tanaka, Hiroko, additional, Suzuki, Hiromichi, additional, Sato, Yusuke, additional, Shiozawa, Yusuke, additional, Yoshizato, Tetsuichi, additional, Yoshida, Kenichi, additional, Makishima, Hideki, additional, Ma, Guangyong, additional, Nosaka, Kisato, additional, Hishizawa, Masakatsu, additional, Itonaga, Hidehiro, additional, Imaizumi, Yoshitaka, additional, Munakata, Wataru, additional, Hiromi, Nakamura, additional, Hama, Natsuko, additional, Shide, Kotaro, additional, Kubuki, Yoko, additional, Hidaka, Tomonori, additional, Kameda, Takuro, additional, Nakamaki, Tsuyoshi, additional, Ishiyama, Ken, additional, Miyawaki, Shuichi, additional, Tobinai, Kensei, additional, Miyazaki, Yasushi, additional, Takaori-Kondo, Akifumi, additional, Watanabe, Toshiki, additional, Shibata, Tatsuhiro, additional, Matsuoka, Masao, additional, Miyano, Satoru, additional, Shimoda, Kazuya, additional, and Ogawa, Seishi, additional

Published
2015
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14. Landscape of Genetic Alterations in Adult T-Cell Leukemia/Lymphoma

Author

Kataoka, Keisuke, primary, Nagata, Yasunobu, additional, Kitanaka, Akira, additional, Totoki, Yasushi, additional, Yasunaga, Jun-ichirou, additional, Kotani, Shinichi, additional, Sato-Otsubo, Aiko, additional, Sanada, Masashi, additional, Shiraishi, Yuichi, additional, Shimamura, Teppei, additional, Chiba, Kenichi, additional, Tanaka, Hiroko, additional, Suzuki, Hiromichi, additional, Sato, Yusuke, additional, Shiozawa, Yusuke, additional, Yoshizato, Tetsuichi, additional, Kon, Ayana, additional, Yoshida, Kenichi, additional, Hishizawa, Masakatsu, additional, Munakata, Wataru, additional, Nakamura, Hiromi, additional, Hama, Natsuko, additional, Shide, Kotaro, additional, Kubuki, Yoko, additional, Hidaka, Tomonari, additional, Kameda, Takuro, additional, Ishiyama, Ken, additional, Miyawaki, Shuichi, additional, Ishii, Ryohei, additional, Nureki, Osamu, additional, Nagae, Genta, additional, Aburatani, Hiroyuki, additional, Miyano, Satoru, additional, Takaori-Kondo, Akifumi, additional, Watanabe, Toshiki, additional, Matsuoka, Masao, additional, Shibata, Tatsuhiro, additional, Shimoda, Kazuya, additional, and Ogawa, Seishi, additional

Published
2014
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15. Novel Biological Effects and Distinct Patterns of Rhoa Mutations in Adult T-Cell Leukemia/Lymphoma and Angioimmunoblastic T Cell Lymphoma

Author

Nagata, Yasunobu, primary, Enami, Terukazu, additional, Kontani, Kenji, additional, Kataoka, Keisuke, additional, Sakata-Yanagimoto, Mamiko, additional, Kitanaka, Akira, additional, Sato, Aiko, additional, Shiraishi, Yuichi, additional, Chiba, Kenichi, additional, Tanaka, Hiroko, additional, Shiozawa, Yusuke, additional, Yoshizato, Tetsuichi, additional, Kon, Ayana, additional, Yoshida, Kenichi, additional, Sanada, Masashi, additional, Ishiyama, Ken, additional, Miyawaki, Shuichi, additional, Ishii, Ryohei, additional, Nureki, Osamu, additional, Miyano, Satoru, additional, Shimoda, Kazuya, additional, Watanabe, Toshiki, additional, Katada, Toshiaki, additional, Chiba, Shigeru, additional, and Ogawa, Seishi, additional

Published
2014
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16. Molecular Characterization Of Adult T-Cell Leukemia/Lymphoma

Author

Nagata, Yasunobu, primary, Kitanaka, Akira, additional, Sanada, Masashi, additional, Sato, Aiko, additional, Okuno, Yusuke, additional, Shiraishi, Yuichi, additional, Chiba, Kenichi, additional, Tanaka, Hiroko, additional, Yoshizato, Tetsuichi, additional, Kon, Ayana, additional, Yoshida, Kenichi, additional, Ishiyama, Ken, additional, Miyawaki, Shuichi, additional, Miyano, Satoru, additional, Shimoda, Kazuya, additional, and Ogawa, Seishi, additional

Published
2013
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18. Prognostic Factor, Including Relative Dose Intensity, For Adult T-Cell Leukemia/Lymphoma In Clinical Practice

Author

Kamiunten, Ayako, primary, Kitanaka, Akira, additional, Kubuki, Yoko, additional, Hidaka, Tomonori, additional, Shide, Kotaro, additional, Kameda, Takuro, additional, Sekine, Masaaki, additional, Yamashita, Kiyoshi, additional, Matsuoka, Hitoshi, additional, Kawano, Hiroshi, additional, Toyama, Takanori, additional, Satou, Seiichi, additional, Maeda, Kouichi, additional, Ishizaki, Junzo, additional, and Shimoda, Kazuya, additional

Published
2013
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20. TET2 Mutations Revealed by Whole Genome Sequencing in Adult T-Cell Leukemia.

Author

Nagata, Yasunobu, primary, Sato, Aiko, additional, Kon, Ayana, additional, Okuno, Yusuke, additional, Chiba, Kenichi, additional, Tanaka, Hiroko, additional, Shiraishi, Yuichi, additional, Yoshida, Kenichi, additional, Sanada, Masashi, additional, Utsunomiya, Atae, additional, Yamaguchi, Kazunari, additional, Oshima, Kouichi, additional, Miyawaki, Shuichi, additional, Kitanaka, Akira, additional, Miyano, Satoru, additional, Watanabe, Toshiki, additional, and Ogawa, Seishi, additional

Published
2012
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31. Variegated RHOAmutations in adult T-cell leukemia/lymphoma

Author

Nagata, Yasunobu, Kontani, Kenji, Enami, Terukazu, Kataoka, Keisuke, Ishii, Ryohei, Totoki, Yasushi, Kataoka, Tatsuki R., Hirata, Masahiro, Aoki, Kazuhiro, Nakano, Kazumi, Kitanaka, Akira, Sakata-Yanagimoto, Mamiko, Egami, Sachiko, Shiraishi, Yuichi, Chiba, Kenichi, Tanaka, Hiroko, Shiozawa, Yusuke, Yoshizato, Tetsuichi, Suzuki, Hiromichi, Kon, Ayana, Yoshida, Kenichi, Sato, Yusuke, Sato-Otsubo, Aiko, Sanada, Masashi, Munakata, Wataru, Nakamura, Hiromi, Hama, Natsuko, Miyano, Satoru, Nureki, Osamu, Shibata, Tatsuhiro, Haga, Hironori, Shimoda, Kazuya, Katada, Toshiaki, Chiba, Shigeru, Watanabe, Toshiki, and Ogawa, Seishi

Abstract

Adult T-cell leukemia/lymphoma (ATLL) is a distinct form of peripheral T-cell lymphoma with poor prognosis, which is caused by the human T-lymphotropic virus type 1 (HTLV-1). In contrast to the unequivocal importance of HTLV-1 infection in the pathogenesis of ATLL, the role of acquired mutations in HTLV-1 infected T cells has not been fully elucidated, with a handful of genes known to be recurrently mutated. In this study, we identified unique RHOAmutations in ATLL through whole genome sequencing of an index case, followed by deep sequencing of 203 ATLL samples. RHOAmutations showed distinct distribution and function from those found in other cancers. Involving 15% (30/203) of ATLL cases, RHOAmutations were widely distributed across the entire coding sequence but almost invariably located at the guanosine triphosphate (GTP)-binding pocket, with Cys16Arg being most frequently observed. Unexpectedly, depending on mutation types and positions, these RHOA mutants showed different or even opposite functional consequences in terms of GTP/guanosine diphosphate (GDP)-binding kinetics, regulation of actin fibers, and transcriptional activation. The Gly17Val mutant did not bind GTP/GDP and act as a dominant negative molecule, whereas other mutants (Cys16Arg and Ala161Pro) showed fast GTP/GDP cycling with enhanced transcriptional activation. These findings suggest that both loss- and gain-of-RHOA functions could be involved in ATLL leukemogenesis. In summary, our study not only provides a novel insight into the molecular pathogenesis of ATLL but also highlights a unique role of variegation of heterologous RHOAmutations in human cancers.

Published
2016
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33. CD38-Mediated Growth Suppression of B-Cell Progenitors Requires Activation of Phosphatidylinositol 3-Kinase and Involves Its Association With the Protein Product of the c-cblProto-Oncogene

Author

Kitanaka, Akira, Ito, Chikako, Nishigaki, Hikari, and Campana, Dario

Abstract

The signaling pathways that arrest the cell cycle and trigger cell death are only partially known. Dimerization of CD38, a 45-kD transmembrane type II glycoprotein highly expressed in immature B cells, inhibits cell growth and causes apoptosis in normal and leukemic B-cell progenitors, but the molecular mechanisms underlying these cellular responses are unknown. In the present study, we found that CD38 ligation in the immature B-cell lines 380, REH, and RS4;11 caused rapid tyrosine phosphorylation of the protein product of the proto-oncogene c-cbl.Dimerization of CD38 was accompanied by the association of cblwith the p85 subunit of phosphatidylinositol 3-kinase (PI 3-K), resulting in markedly increased PI 3-K activity in antiphosphotyrosine and anti-cblimmunoprecipitates. Wortmannin and LY294002, two potent inhibitors of PI 3-K, rescued immature B cells from CD38-mediated growth suppression. This effect was observed not only in model B-cell lines, but also in cultures of leukemic lymphoblasts from patients, and in normal bone marrow B-cell progenitors as well. Concentrations of inhibitors that reversed cellular responses to CD38 significantly decreased PI 3-K activity. By contrast, rapamycin, a p70 S6-kinase inhibitor, did not rescue immature B cells from CD38-mediated suppression. These results suggest that PI 3-K activity is essential for CD38-mediated inhibition of lymphopoiesis and that cbland PI 3-K are regulatory molecules whose activation can result in suppression of cell proliferation and apoptosis in immature lymphoid cells.

Published
1996
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34. Malignant Progression of an MDS-Derived Cell Line Serves As an in VitroModel for the Leukemic Evolution of MDS

Author

Kida, Jun-ichiro, Tsujioka, Takayuki, Suemori, Shin-ichiro, Okamoto, Shuichiro, Sakakibara, Kanae, Yamauchi, Takahiro, Kitanaka, Akira, Tohyama, Yumi, and Tohyama, Kaoru

Abstract

Myelodysplastic syndromes (MDS) have a risk of progression to acute myeloid leukemia (AML), but the deterioration mechanisms of MDS and the alteration points still remain to be elucidated. We previously established a myelodysplastic cell line, MDS92 from the bone marrow of an MDS patient, and after a long-term interleukin(IL)-3-containing culture of MDS92, five blastic sublines including MDS-L were isolated. From MDS-L, we obtained two sublines, MDS-L-2007 and MDS-LGF after culture in the presence and absence of IL-3, respectively. To investigate the mechanism of leukemic evolution, we applied a next-generation sequencing (NGS) to the series of cell lines for comprehensive, comparative exome analyses, and searched for the origin of mutations by ultra-deep target sequencing of the original patient bone marrow.

Published
2018
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35. Novel Biological Effects and Distinct Patterns of RhoaMutations in Adult T-Cell Leukemia/Lymphoma and Angioimmunoblastic T Cell Lymphoma

Author

Nagata, Yasunobu, Enami, Terukazu, Kontani, Kenji, Kataoka, Keisuke, Sakata-Yanagimoto, Mamiko, Kitanaka, Akira, Sato, Aiko, Shiraishi, Yuichi, Chiba, Kenichi, Tanaka, Hiroko, Shiozawa, Yusuke, Yoshizato, Tetsuichi, Kon, Ayana, Yoshida, Kenichi, Sanada, Masashi, Ishiyama, Ken, Miyawaki, Shuichi, Ishii, Ryohei, Nureki, Osamu, Miyano, Satoru, Shimoda, Kazuya, Watanabe, Toshiki, Katada, Toshiaki, Chiba, Shigeru, and Ogawa, Seishi

Abstract

Adult T-cell leukemia/lymphoma (ATL) is a distinct form of peripheral T-cell lymphoma (PTCL). ATL is initiated by immortalization of T-cells by human T-lymphotropic virus type I (HTLV-1) infection during early infancy, followed by an accumulation of multiple genetic hits to develop leukemia. However, little has been known about these genetic hits. Recently, frequent somatic mutations in RHOA, DNMT3A, IDH2and TET2have been reported in angioimmunoblastic T cell lymphoma (AITL) and PTCL not otherwise specified (PTCL-NOS), which are characterized by follicular helper T-cell phenotypes. Most of the RHOAmutations in AITL invariably cause an identical amino acid change (Gly17Val), which was shown to inhibit wild-type RHOA function in a dominant-negative manner. In addition, RHOAmutations have been also identified in gastric cancer and Burkitt lymphoma, with mutational hotspots including Tyr42 and Arg5. Interestingly, some of them were reported as working in a gain-of function manner.

Published
2014
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