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4. Corrigendum to “Comprehensive clinical and molecular characterization of claudin 18.2 expression in advanced gastric or gastroesophageal junction cancer”

Author

Kubota, Y., primary, Kawazoe, A., additional, Mishima, S., additional, Nakamura, Y., additional, Kotani, D., additional, Kuboki, Y., additional, Bando, H., additional, Kojima, T., additional, Doi, T., additional, Yoshino, T., additional, Kuwata, T., additional, and Shitara, K., additional

Published
2024
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5. Phase III trial of short-course radiotherapy followed by CAPOXIRI versus CAPOX in locally advanced rectal cancer: the ENSEMBLE trial

Author

Watanabe, J., primary, Kagawa, Y., additional, Chida, K., additional, Ando, K., additional, Kotani, D., additional, Oba, K., additional, Bando, H., additional, Hojo, H., additional, Shimamoto, S., additional, Sakashita, S., additional, Kuwata, T., additional, Tsuboyama, T., additional, Hosomi, N., additional, Uemura, M., additional, Uehara, K., additional, Ito, M., additional, Oki, E., additional, Takemasa, I., additional, Misugi, E., additional, Sledge, G., additional, Sumani, K., additional, Imoto, S., additional, Kato, T., additional, and Yoshino, T., additional

Published
2023
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11. Generating Polygons with Triangles

Author

Kuwata, T., Maehara, H., Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Weikum, Gerhard, Series editor, Akiyama, Jin, editor, Ito, Hiro, editor, and Sakai, Toshinori, editor

Published
2014
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16. Completion of JT-60SA construction and contribution to ITER

Author

Kamada Y., Di Pietro E., Hanada M., Barabaschi P., Ide S., Davis S., Yoshida M., Giruzzi G., Sozzi C., Abdel Maksoud W., Abe H., Aiba N., Akiyama T., Ayllon-Guerola J., Arai T., Artaud J. -F., Asakura N., Ashikawa N., Balbinot L., Bando T., Baulaigue O., Belonohy E., Bin W., Bombarda F., Bolzonella T., Bonne F., Bonotto M., Botija J., Cabrera-Perez S., Cardella A., Carraro L., Cavalier J., Chernyshova M., Chiba S., Clement-Lorenzo S., Cocilovo V., Coda S., Coelho R., Coffey I., Collin B., Corato V., Cucchiaro A., Czarski T., Dairaku M., Day C., de la Luna E., De Tommasi G., Decool P., Di Pace L., Dibon M., Disset G., Ejiri A., Endo Y., Ezumi N., Falchetto G., Fassina A., Fejoz P., Ferro A., Fietz W., Figini L., Fornal T., Frello G., Fujita T., Fukuda T., Fukui K., Fukumoto M., Furukawa M., Futatani S., Gabellieri L., Gaio E., Galazka K., Garcia J., Garcia-Dominguez J., Garcia-Lopez J., Garcia-Munoz M., Garzotti L., Gasparini F., Gharafi S., Giacomelli L., Ginoulhiac G., Giudicotti L., Guillen Gonzalez R., Hajnal N., Hall S., Hamada K., Hanada K., Hasegawa K., Hatae T., Hatakeyama S., Hauer V., Hayashi N., Hayashi T., Heller R., Higashijima S., Hinata J., Hiranai S., Hiratsuka J., Hiwatari R., Hoa C., Homma H., Honda A., Honda M., Horiike H., Hoshino K., Hurzlmeier H., Iafrati M., Ibano K., Ichige H., Ichikawa M., Ichimura M., Ida K., Idei H., Iijima T., Iio S., Ikeda R., Ikeda Y., Imai T., Imazawa R., Inagaki S., Inomoto M., Inoue S., Isayama A., Ishida S., Ishii Y., Isobe M., Janky F., Joffrin E., Jokinen A., Kado S., Kajita S., Kajiwara K., Kamata I., Kaminaga A., Kamiya K., Kanapienyte D., Kashiwa Y., Kashiwagi M., Katayama K., Kawamata Y., Kawamura G., Kawano K., Kawashima H., Kin F., Kitajima S., Kiyono K., Kizu K., Kobayashi K., Kobayashi M., Kobayashi S., Kobayashi T., Kocsis G., Koide Yo., Koide Yu., Kojima A., Kokusen S., Komuro K., Konishi S., Kovacsik A., Ksiazek I., Kubkowska M., Kuhner G., Kuramochi M., Kurihara K., Kurki-Suonio T., Kurniawan A. B., Kuwata T., Lacroix B., Lamaison V., Lampasi A., Lang P., Lauber P., Lawson K., Louzguiti A., Maekawa R., Maekawa T., Maeyama S., Maffia G., Maget P., Mailloux J., Maione I., Maistrello A., Malinowski K., Marchiori G., Marechal J. -L., Massaut V., Masuzaki S., Matsunaga G., Matsunaga S., Mayri Ch., Mattei M., Medrano M., Mele A., Meyer I., Michel F., Minami T., Miyata Y., Miyazawa J., Miyo Y., Mizuuchi T., Mogaki K., Morales J., Moreau P., Mori M., Morisaki T., Morishima S., Moriyama S., Moro A., Murakami H., Murayama M., Murakami S., Nagasaki K., Naito O., Nakamura S., Nakano T., Nakashima Y., Nardino V., Narita E., Narushima Y., Natsume K., Nemoto S., Neu R., Nicollet S., Nishikawa M., Nishimura S., Nishiura M., Nishiyama T., Nocente M., Nobuta Y., Novello L., Nunio F., Ochoa S., Ogawa T., Ogawa Y., Ohdachi S., Ohmori Y., Ohno N., Ohtani Y., Ohzeki M., Oishi T., Okano F., Okano J., Okano K., Onishi Y., Osakabe M., Oshima T., Ostuni V., Oya M., Oya Y., Oyama N., Ozeki T., Pasqualotto R., Pelli S., Peretti E., Phillips G., Piccinni C., Pigatto L., Pironti A., Pizzuto A., Plockl B., Polli G., Poncet J. -M., Ponsot P., Puiatti M., Radloff D., Raimondi V., Ramos F., Rancsik P., Ricci D., Ricciarini S., Rincon E., Romano A., Rossi P., Roussel P., Rubino G., Saeki H., Sagara A., Sakakibara S., Sakamoto H., Sakamoto M., Sakamoto Y., Sakasai A., Sakata S., Sakuma T., Sakurai S., Salanon B., Salmi A., Sannazzaro G., Sano R., Sanpei A., Sasajima T., Sasaki S., Sasao H., Sato F., Sato M., Sawahata M., Scherber A., Scully S., Seki M., Seki S., Shibama Y., Shibata Y., Shikama T., Shimada K., Shimono M., Shinde J., Shinya T., Shinohara K., Shirai H., Shiraishi J., Soare S., Soleto A., Someya Y., Streciwilk-Kowalska E., Strobel H., Sueoka M., Sukegawa A., Sulistyanintyas D., Sumida S., Sunaoshi H., Suzuki H., Suzuki M., Suzuki S., Suzuki T., Suzuki Y., Svoboda J., Szabolics T., Szepesi T., Takahashi K., Takase Y., Takechi M., Takeda K., Takeiri Y., Takenaga H., Taliercio C., Tamura N., Tanaka H., Tanaka K., Tani K., Tanigawa H., Tardocchi M., Terakado A., Terakado M., Terakado T., Teuchner B., Tilia B., Tobita K., Toi K., Toida N., Tojo H., Tokitani M., Tokuzawa T., Tormarchio V., Tomine M., Torre A., Totsuka T., Tsuchiya K., Tsujii N., Tsuru D., Tsutsui H., Uchida M., Ueda Y., Uno J., Urano H., Usui K., Utoh H., Valisa M., Vallar M., Vallcorba-Carbonell R., Vallet J. -C., Varela J., Vega J., Verrecchia M., Vieillard L., Villone F., Vincenzi P., Wada K., Wada R., Wakatsuki T., Wanner M., Watanabe F., Watanabe K., Wauters T., Wiesen S., Wischmeier M., Yagi M., Yagyu J., Yajima M., Yokooka S., Yokoyama M., Yamamoto S., Yamanaka H., Yamauchi K., Yamauchi Y., Yamazaki H., Yamazaki K., Yamazaki R., Yamoto S., Yanagi S., Yanagihara K., Yoshizawa N., Zani L., Zito P., Kamada, Y., Di Pietro, E., Hanada, M., Barabaschi, P., Ide, S., Davis, S., Yoshida, M., Giruzzi, G., Sozzi, C., Abdel Maksoud, W., Abe, H., Aiba, N., Akiyama, T., Ayllon-Guerola, J., Arai, T., Artaud, J. -F., Asakura, N., Ashikawa, N., Balbinot, L., Bando, T., Baulaigue, O., Belonohy, E., Bin, W., Bombarda, F., Bolzonella, T., Bonne, F., Bonotto, M., Botija, J., Cabrera-Perez, S., Cardella, A., Carraro, L., Cavalier, J., Chernyshova, M., Chiba, S., Clement-Lorenzo, S., Cocilovo, V., Coda, S., Coelho, R., Coffey, I., Collin, B., Corato, V., Cucchiaro, A., Czarski, T., Dairaku, M., Day, C., de la Luna, E., De Tommasi, G., Decool, P., Di Pace, L., Dibon, M., Disset, G., Ejiri, A., Endo, Y., Ezumi, N., Falchetto, G., Fassina, A., Fejoz, P., Ferro, A., Fietz, W., Figini, L., Fornal, T., Frello, G., Fujita, T., Fukuda, T., Fukui, K., Fukumoto, M., Furukawa, M., Futatani, S., Gabellieri, L., Gaio, E., Galazka, K., Garcia, J., Garcia-Dominguez, J., Garcia-Lopez, J., Garcia-Munoz, M., Garzotti, L., Gasparini, F., Gharafi, S., Giacomelli, L., Ginoulhiac, G., Giudicotti, L., Guillen Gonzalez, R., Hajnal, N., Hall, S., Hamada, K., Hanada, K., Hasegawa, K., Hatae, T., Hatakeyama, S., Hauer, V., Hayashi, N., Hayashi, T., Heller, R., Higashijima, S., Hinata, J., Hiranai, S., Hiratsuka, J., Hiwatari, R., Hoa, C., Homma, H., Honda, A., Honda, M., Horiike, H., Hoshino, K., Hurzlmeier, H., Iafrati, M., Ibano, K., Ichige, H., Ichikawa, M., Ichimura, M., Ida, K., Idei, H., Iijima, T., Iio, S., Ikeda, R., Ikeda, Y., Imai, T., Imazawa, R., Inagaki, S., Inomoto, M., Inoue, S., Isayama, A., Ishida, S., Ishii, Y., Isobe, M., Janky, F., Joffrin, E., Jokinen, A., Kado, S., Kajita, S., Kajiwara, K., Kamata, I., Kaminaga, A., Kamiya, K., Kanapienyte, D., Kashiwa, Y., Kashiwagi, M., Katayama, K., Kawamata, Y., Kawamura, G., Kawano, K., Kawashima, H., Kin, F., Kitajima, S., Kiyono, K., Kizu, K., Kobayashi, K., Kobayashi, M., Kobayashi, S., Kobayashi, T., Kocsis, G., Koide, Yo., Koide, Yu., Kojima, A., Kokusen, S., Komuro, K., Konishi, S., Kovacsik, A., Ksiazek, I., Kubkowska, M., Kuhner, G., Kuramochi, M., Kurihara, K., Kurki-Suonio, T., Kurniawan, A. B., Kuwata, T., Lacroix, B., Lamaison, V., Lampasi, A., Lang, P., Lauber, P., Lawson, K., Louzguiti, A., Maekawa, R., Maekawa, T., Maeyama, S., Maffia, G., Maget, P., Mailloux, J., Maione, I., Maistrello, A., Malinowski, K., Marchiori, G., Marechal, J. -L., Massaut, V., Masuzaki, S., Matsunaga, G., Matsunaga, S., Mayri, Ch., Mattei, M., Medrano, M., Mele, A., Meyer, I., Michel, F., Minami, T., Miyata, Y., Miyazawa, J., Miyo, Y., Mizuuchi, T., Mogaki, K., Morales, J., Moreau, P., Mori, M., Morisaki, T., Morishima, S., Moriyama, S., Moro, A., Murakami, H., Murayama, M., Murakami, S., Nagasaki, K., Naito, O., Nakamura, S., Nakano, T., Nakashima, Y., Nardino, V., Narita, E., Narushima, Y., Natsume, K., Nemoto, S., Neu, R., Nicollet, S., Nishikawa, M., Nishimura, S., Nishiura, M., Nishiyama, T., Nocente, M., Nobuta, Y., Novello, L., Nunio, F., Ochoa, S., Ogawa, T., Ogawa, Y., Ohdachi, S., Ohmori, Y., Ohno, N., Ohtani, Y., Ohzeki, M., Oishi, T., Okano, F., Okano, J., Okano, K., Onishi, Y., Osakabe, M., Oshima, T., Ostuni, V., Oya, M., Oya, Y., Oyama, N., Ozeki, T., Pasqualotto, R., Pelli, S., Peretti, E., Phillips, G., Piccinni, C., Pigatto, L., Pironti, A., Pizzuto, A., Plockl, B., Polli, G., Poncet, J. -M., Ponsot, P., Puiatti, M., Radloff, D., Raimondi, V., Ramos, F., Rancsik, P., Ricci, D., Ricciarini, S., Rincon, E., Romano, A., Rossi, P., Roussel, P., Rubino, G., Saeki, H., Sagara, A., Sakakibara, S., Sakamoto, H., Sakamoto, M., Sakamoto, Y., Sakasai, A., Sakata, S., Sakuma, T., Sakurai, S., Salanon, B., Salmi, A., Sannazzaro, G., Sano, R., Sanpei, A., Sasajima, T., Sasaki, S., Sasao, H., Sato, F., Sato, M., Sawahata, M., Scherber, A., Scully, S., Seki, M., Seki, S., Shibama, Y., Shibata, Y., Shikama, T., Shimada, K., Shimono, M., Shinde, J., Shinya, T., Shinohara, K., Shirai, H., Shiraishi, J., Soare, S., Soleto, A., Someya, Y., Streciwilk-Kowalska, E., Strobel, H., Sueoka, M., Sukegawa, A., Sulistyanintyas, D., Sumida, S., Sunaoshi, H., Suzuki, H., Suzuki, M., Suzuki, S., Suzuki, T., Suzuki, Y., Svoboda, J., Szabolics, T., Szepesi, T., Takahashi, K., Takase, Y., Takechi, M., Takeda, K., Takeiri, Y., Takenaga, H., Taliercio, C., Tamura, N., Tanaka, H., Tanaka, K., Tani, K., Tanigawa, H., Tardocchi, M., Terakado, A., Terakado, M., Terakado, T., Teuchner, B., Tilia, B., Tobita, K., Toi, K., Toida, N., Tojo, H., Tokitani, M., Tokuzawa, T., Tormarchio, V., Tomine, M., Torre, A., Totsuka, T., Tsuchiya, K., Tsujii, N., Tsuru, D., Tsutsui, H., Uchida, M., Ueda, Y., Uno, J., Urano, H., Usui, K., Utoh, H., Valisa, M., Vallar, M., Vallcorba-Carbonell, R., Vallet, J. -C., Varela, J., Vega, J., Verrecchia, M., Vieillard, L., Villone, F., Vincenzi, P., Wada, K., Wada, R., Wakatsuki, T., Wanner, M., Watanabe, F., Watanabe, K., Wauters, T., Wiesen, S., Wischmeier, M., Yagi, M., Yagyu, J., Yajima, M., Yokooka, S., Yokoyama, M., Yamamoto, S., Yamanaka, H., Yamauchi, K., Yamauchi, Y., Yamazaki, H., Yamazaki, K., Yamazaki, R., Yamoto, S., Yanagi, S., Yanagihara, K., Yoshizawa, N., Zani, L., and Zito, P.

Subjects
assembly, Cryostat, Nuclear and High Energy Physics, Materials science, Tokamak, Nuclear engineering, Plasma, Condensed Matter Physics, Field coil, ITER risk mitigation, Overcurrent, law.invention, Control theory, law, Electromagnetic coil, research plan, broader approach, Voltage
Abstract

Construction of the JT-60SA tokamak was completed on schedule in March 2020. Manufacture and assembly of all the main tokamak components satisfied technical requirements, including dimensional accuracy and functional performances. Development of the plasma heating systems and diagnostics have also progressed, including the demonstration of the favourable electron cyclotron range of frequency (ECRF) transmission at multiple frequencies and the achievement of long sustainment of a high-energy intense negative ion beam. Development of all the tokamak operation control systems has been completed, together with an improved plasma equilibrium control scheme suitable for superconducting tokamaks including ITER. For preparation of the tokamak operation, plasma discharge scenarios have been established using this advanced equilibrium controller. Individual commissioning of the cryogenic system and the power supply system confirmed that these systems satisfy design requirements including operational schemes contributing directly to ITER, such as active control of heat load fluctuation of the cryoplant, which is essential for dynamic operation in superconducting tokamaks. The integrated commissioning (IC) is started by vacuum pumping of the vacuum vessel and cryostat, and then moved to cool-down of the tokamak and coil excitation tests. Transition to the super-conducting state was confirmed for all the TF, EF and CS coils. The TF coil current successfully reached 25.7 kA, which is the nominal operating current of the TF coil. For this nominal toroidal field of 2.25 T, ECRF was applied and an ECRF plasma was created. The IC was, however, suspended by an incident of over current of one of the superconducting equilibrium field coil and He leakage caused by insufficient voltage holding capability at a terminal joint of the coil. The unique importance of JT-60SA for H-mode and high-β steady-state plasma research has been confirmed using advanced integrated modellings. These experiences of assembly, IC and plasma operation of JT-60SA contribute to ITER risk mitigation and efficient implementation of ITER operation.

Published
2022

26. Effect of Tumor Expressions of Cancer Stem Cell Markers (ALDH1 & CD133) on Disease-Free Intervals (DFI) and Survival in Lung Adenocarcinoma Patients

Author

Oyama, T., primary, Uramoto, H., additional, Shinohara, S., additional, Kuwata, T., additional, Imanishi, N., additional, Kuroda, K., additional, So, T., additional, Miyata, T., additional, Yamashita, N., additional, Yoshimatsu, T., additional, Hanagiri, T., additional, Gotoh, A., additional, Osaki, T., additional, Nakanishi, R., additional, and Tanaka, F., additional

Published
2020
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41. P3.09-06 The Link Between Tumor Promoting Fibrous Microenvironment and Immunosuppressive Microenvironment in Stage I Lung Adenocarcinoma

Author

Sakai, T., primary, Aokage, K., additional, Neri, S., additional, Nakamura, H., additional, Okada, S., additional, Miyoshi, T., additional, Tane, K., additional, Sugano, M., additional, Kojima, M., additional, Fujii, S., additional, Kuwata, T., additional, Ochiai, A., additional, Tsuboi, M., additional, and Ishii, G., additional

Published
2018
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42. The nationwide cancer genome screening project in Japan, SCRUM-Japan GI-SCREEN: Efficient identification of cancer genome alterations in advanced esophageal cancer

Author

Kato, K., primary, Kojima, T., additional, Saeki, H., additional, Hara, H., additional, Kajiwara, T., additional, Hironaka, S., additional, Nakatsumi, H., additional, Kadowaki, S., additional, Kagawa, Y., additional, Esaki, T., additional, Moriwaki, T., additional, Kobayashi, T., additional, Izawa, N., additional, Nomura, S., additional, Kuwata, T., additional, Fujii, S., additional, Okamoto, W., additional, Shitara, K., additional, Ohtsu, A., additional, and Yoshino, T., additional

Published
2018
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43. The nationwide cancer genome screening project in Japan, SCRUM Japan GISCREEN: Efficient identification of cancer genome alterations in advanced biliary tract cancer

Author

Morizane, C., primary, Komatsu, Y., additional, Takahashi, H., additional, Ueno, M., additional, Furuse, J., additional, Kudo, T., additional, Itoh, S., additional, Shimizu, S., additional, Nakamura, K., additional, Kamata, K., additional, Ohtsubo, K., additional, Mizukami, T., additional, Kagawa, Y., additional, Nomura, S., additional, Kuwata, T., additional, Fujii, S., additional, Okamoto, W., additional, Shitara, K., additional, Ohtsu, A., additional, and Yoshino, T., additional

Published
2018
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44. The nationwide cancer genome screening project in Japan, SCRUM-Japan GI-SCREEN: Efficient identification of cancer genome alterations in advanced pancreatic cancer

Author

Izawa, N., primary, Morizane, C., additional, Takahashi, H., additional, Ueno, M., additional, Kawamoto, Y., additional, Okano, N., additional, Shimizu, S., additional, Sudo, K., additional, Itoh, S., additional, Asagi, A., additional, Kagawa, Y., additional, Kamata, K., additional, Kudo, T., additional, Nomura, S., additional, Kuwata, T., additional, Fujii, S., additional, Okamoto, W., additional, Shitara, K., additional, Ohtsu, A., additional, and Yoshino, T., additional

Published
2018
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46. Timing of Craniotomy in a Patient With Multiple Trauma Including Head Injury -Case Report

Author

Ichiro Kamei, Toshihide Tsujimoto, Michio Yabumoto, Toru Itakura, Genhachi Hyotani, Ryo Yoshimura, Kuwata T, Junya Fukai, and Masaki Raimura

Subjects
medicine.medical_specialty, business.industry, medicine.medical_treatment, Head injury, Abdominal cavity, medicine.disease, Surgery, Pulmonary contusion, medicine.anatomical_structure, Blunt, Laparotomy, Anesthesia, medicine, Abdomen, Decompressive craniectomy, Neurology (clinical), business, Craniotomy
Abstract

A 7-year-old boy suffered blunt multiple injuries to the head, face, chest, and abdomen in a motor vehicle accident. On admission he had impaired consciousness and dyspnea. Radiographic studies revealed facial fracture and pulmonary contusion. Shortly after admission, he fell into shock due to intraabdominal bleeding. Laparotomy revealed spleen rupture. His vital signs remained unstable and bloody drainage from the abdominal cavity continued after surgery. Computed tomography showed traumatic intracerebral hematoma in the right temporal lobe, enlarging and compressing the brainstem. Abdominal reoperation was performed first to control the bleeding and stabilize the hemodynamics, disclosing renal laceration. Then evacuation of the intracerebral hematoma and decompressive craniectomy was performed. Postoperatively, his hemodynamics were stabilized. Clinical course was uneventful and neurological deficits gradually improved. Three months after the trauma, the patient was discharged on foot. This case emphasizes the importance of hemodynamic stability in decisions of neurosurgical indication and timing in patients with multiple trauma including head injury.

Published
2009

48. The nationwide cancer genome screening project in Japan SCRUM-Japan GI-SCREEN: Efficient identification of cancer genome alterations in advanced pancreatic cancer

Author

Naruge, D., primary, Morizane, C., additional, Ueno, M., additional, Takahashi, H., additional, Kawamoto, Y., additional, Sudo, K., additional, Shimizu, S., additional, Nakajima, T.E., additional, Itoh, S., additional, Ishii, H., additional, Kato, T., additional, Kudo, T., additional, Izumi, M., additional, Sudo, T., additional, Nomura, S., additional, Kuwata, T., additional, Fujii, S., additional, Shitara, K., additional, Ohtsu, A., additional, and Yoshino, T., additional

Published
2017
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50. MEIS1-mediated transactivation of synaptotagmin-like 1 promotes CXCL12/CXCR4 signaling and leukemogenesis

Author

Yokoyama, T. (Takashi), Nakatake, M. (Mayuka), Kuwata, T. (Takeshi), Couzinet, A. (Arnaud), Goitsuka, R. (Ryo), Tsutsumi, S. (Shuichi), Aburatani, H. (Hiroyuki), Valk, P.J.M. (Peter), Delwel, H.R. (Ruud), Nakamura, T. (Takuro), Yokoyama, T. (Takashi), Nakatake, M. (Mayuka), Kuwata, T. (Takeshi), Couzinet, A. (Arnaud), Goitsuka, R. (Ryo), Tsutsumi, S. (Shuichi), Aburatani, H. (Hiroyuki), Valk, P.J.M. (Peter), Delwel, H.R. (Ruud), and Nakamura, T. (Takuro)

Abstract

The TALE-class homeoprotein MEIS1 specifically collaborates with HOXA9 to drive myeloid leukemogenesis. Although MEIS1 alone has only a moderate effect on cell proliferation in vitro, it is essential for the development of HOXA9-induced leukemia in vivo. Here, using murine models of leukemogenesis, we have shown that MEIS1 promotes leukemic cell homing and engraftment in bone marrow and enhances cell-cell interactions and cytokine-mediated cell migration. We analyzed global DNA binding of MEIS1 in leukemic cells as well as gene expression alterations in MEIS1-deficent cells and identified synaptotagmin-like 1 (Sytl1, also known as Slp1) as the MEIS1 target gene that cooperates with Hoxa9 in leukemogenesis. Replacement of SYTL1 in MEIS1-deficent cells restored both cell migration and engraftment. Further analysis revealed that SYTL1 promotes cell migration via activation of the CXCL12/CXCR4 axis, as SYTL1 determines intracellular trafficking of CXCR4. Together, our results reveal that MEIS1, through induction of SYTL1, promotes leukemogenesis and supports leukemic cell homing and engraftment, facilitating interactions between leukemic cells and bone marrow stroma.

Published
2016
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