Evaluation of iron-sulfur proteins in hematopoietic cells through anamorsin
Project/Area Number |
19K08861
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 54010:Hematology and medical oncology-related
|
Research Institution | Osaka University |
Principal Investigator |
|
Co-Investigator(Kenkyū-buntansha) |
野崎 健司 大阪大学, 医学部附属病院, 医員 (00836413)
横田 貴史 大阪大学, 医学系研究科, 准教授 (60403200)
|
Project Period (FY) |
2019-04-01 – 2022-03-31
|
Project Status |
Completed (Fiscal Year 2021)
|
Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
Keywords | アナモルシン / 鉄・硫黄クラスター / アポトーシス / 遺伝子欠損マウス / 条件付き遺伝子欠損マウス / Bリンパ球 / 造血幹細胞 / RNA-Seq / 鉄過剰 / 骨髄異形成症候群 / 遺伝子改変マウス |
Outline of Research at the Start |
アナモルシン(Anamorsin, AM)は、細胞質内の鉄・硫黄(Fe-S)クラスターを形成するのに必須の分子であることが明らかとなった。AMは、Fe-Sクラスターを有する蛋白群には必須の分子であり、AMが欠損すると、Fe-Sクラスター蛋白の機能が低下し、細胞の生存・増殖・分化などに影響を認めることを明らかにしてきた。また、AMが欠損すると細胞内に自由鉄が蓄積し、それによる活性酸素種(ROS)の蓄積、さらにアポトーシスの増加を認めるようになる。本研究では、鉄過剰状態における造血幹細胞の生存・増殖・分化の異常について、AM遺伝子改変マウスの細胞を用いることにより、AMの機能を中心に解析する。
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Outline of Final Research Achievements |
Anamorsin (AM) was cloned as a cell-death-defying factor. AM-deficient mice are embryonic lethal. To overcome the embryonic lethality, we generated AM conditional KO (AMflox/flox) mice. CD19-Cre/AMflox/flox mice, with AM deleted specifically in CD19+ B cells, exhibited fewer B220+ B cells in spleen, peripheral blood, and LN. CD19-Cre/AMflox/flox mice showed significantly fewer follicular type I (FO-I) cells, which are the most matured FO-B cells, and greater apoptotic cell accumulation in spleen. This suggested that AM deficiency affected terminal differentiation of B cells by increased apoptosis. Furthermore, CD19-Cre/AMflox/flox mice lacked splenic CD19+B220-/low cells. The reduction of p38MAPK, the downstream molecule of BCR signaling, in CD19-Cre/AMflox/flox mice might account for the lack of FO-I cells and splenic CD19+B220-/low cells. Overall, our results suggest that AM plays essential roles in B-cell terminal differentiation.
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Academic Significance and Societal Importance of the Research Achievements |
AMは鉄・硫黄(Fe-S)クラスター形成に関与する分子であることが明らかとなっている。Fe-Sクラスター蛋白は遺伝子の発現制御、DNA修復、光合成などのエネルギー代謝など様々な細胞機能に関与していることが知られているが、Fe-Sクラスター形成がB細胞の成熟分化に関連している報告はこれまでなく、今回の発見は興味深いものと考える。
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Report
(4 results)
Research Products
(98 results)
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[Presentation] Nobel web application predicting patient-specific prognosis in MM from KMF using machine learning.2021
Author(s)
Teruhito Takakuwa, Hiroshi Okamura, Shin-ichi Fuchida, Yuji Shimura, Junya Kanda, Nobuhiko Uoshima, Hirohiko Shibayama, Satoshi Yoshihara, Hideo Yagi, Masayuki Hino, Yuzuru Kanakura, Junya Kuroda, Akifumi Takaori, Chihiro Shimazaki, Itaru Matsumura, Shosaku Nomura
Organizer
第83回日本血液学会学術集会
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[Presentation] Efficacy of elotuzumab plus lenalidomide and dexamethasone for MM: A retrospective analysis from KMF.2021
Author(s)
Shin-ichi Fuchida, Tomoki Ito, Kensuke Ota, Hirohiko Shibayama, Kentaro Fukushima, Hirokazu Tanaka, Yuji Shimura, Kazunori Imada, Hideo Yagi, Satoshi Yoshihara, Masayuki Hino, Naoki Hosen, Akifumi Takaori, Itaru Matsumura, Shosaku Nomura, Chihiro Shimazaki, Junya Kuroda
Organizer
第83回日本血液学会学術集会
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[Presentation] Using ImmunoFISH to determine lymphoid neoplasm relapse after sex-mismatched HSCT or PTLD occurrence2021
Author(s)
Ryumei Kurashige, Masako Kurashige, Yosuke Okada, Kohei Higuchi, Akihisa Hino, Takako Miyamura, Michiko Ichii, Kentaro Fukushima, Makoto Takeuchi, Akihisa Sawada, Masami Inoue, Hirohiko Shibayama, Eiichi Morii, Naoki Hosen
Organizer
第83回日本血液学会学術集会
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[Presentation] A Phase 2b study of an oral HDAC inhibitor HBI-8000 in patients with relapsed or refractory ATL2021
Author(s)
Tatsuro Jo, Atae Utsunomiya, Koji Izutsu, Hirohiko Shibayama, Kazuya Shimoda, Yasushi Takamatsu, Kuniko Takano, Kunihiro Tsukasaki, Jun Taguchi, Kentaro Yonekura, Shinichi Makita, Mireille Gillings, Hiroshi Onogi, Kensei Tobinai
Organizer
第83回日本血液学会学術集会
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[Presentation] Genomic analysis of relapsed AML with RUNX1-RUNX1T1 in a comprehensive NGS multicenter study of AML2021
Author(s)
Seiichiro Katagiri, Daigo Akabane, Akihiko Gotoh, SunGi Chi, Kentaro Fukushima, Hirohiko Shibayama, Naoko Hosono, Takahiro Yamauchi, Naoto Takahashi, Satoshi Iyama, Makoto Nakamura, Yukinobu Nakamura, Koji Izutsu, Hirohiko Yamauchi, Junichiro Yuda, Yosuke Minami
Organizer
第83回日本血液学会学術集会
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[Presentation] Genetic features of AML with MLL-rearrangement and NPM1 mutation: HM-SCREEN-JAPAN012021
Author(s)
SunGi Chi, Kentaro Fukushima, Hirohiko Shibayama, Naoko Hosono, Takahiro Yamauchi, Seiichiro Katagiri, Akihiko Gotoh, Naoto Takahashi, Satoshi Iyama, Makoto Nakamura, Yukinobu Nakamura, Suguru Fukuhara, Koji Izutsu, Hirohiko Yamauchi, Junichiro Yuda, Yosuke Minami
Organizer
第83回日本血液学会学術集会
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[Presentation] Genetic features of AML with normal karyotype: HM-SCREEN-JAPAN012021
Author(s)
SunGi Chi, Masamitsu Yanada, Kazuhito Yamamoto, Naoko Hosono, Takahiro Yamauchi, Kentaro Fukushima, Hirohiko Shibayama, Seiichiro Katagiri, Akihiko Gotoh, Naoto Takahashi, Satoshi Iyama, Makoto Nakamura, Yukinobu Nakamura, Suguru Fukuhara, Koji Izutsu, Hirohiko Yamauchi, Junichiro Yuda, Yosuke Minami
Organizer
第83回日本血液学会学術集会
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[Presentation] Genetic features of AML with IDH1/IDH2 mutation: HM-SCREEN-JAPAN012021
Author(s)
Hirotaka Nakamura, SunGi Chi, Kentaro Fukushima, Hirohiko Shibayama, Naoko Hosono, Takahiro Yamauchi, Seiichiro Katagiri, Akihiko Gotoh, Naoto Takahashi, Satoshi Iyama, Makoto Nakamura, Yukinobu Nakamura, Suguru Fukuhara, Koji Izutsu, Hirohiko Yamauchi, Junichiro Yuda, Yosuke Minami
Organizer
第83回日本血液学会学術集会
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[Presentation] A mutation profiling multicenter study of patients with AML: HM-SCREEN-JAPAN012021
Author(s)
Naoko Hosono, Takahiro Yamauchi, SunGi Chi, Kentaro Fukushima, Hirohiko Shibayama, Seiichiro Katagiri, Akihiko Gotoh, Naoto Takahashi, Satoshi Iyama, Makoto Nakamura, Yukinobu Nakamura, Suguru Fukuhara, Koji Izutsu, Hirohiko Yamauchi, Junichiro Yuda, Yosuke Minami
Organizer
第83回日本血液学会学術集会
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[Presentation] A case of PTCL-NOS with central nervous system involvement successfully treated with oral forodesine.2021
Author(s)
Yukio Doi, Takafumi Yokota, Hirohiko Shibayama, Kana Matsumoto, Masako Kurashige, Kenji Nozaki, Kouki Yoshida, Makiko Suga, Midori Koike, Jun Toda, Keigo Akuta, Akihisa Hino, Tomoaki Ueda, Yasuhiro Nagate, Jiro Fujita, Kentaro Fukushima, Naoki Hosen
Organizer
第83回日本血液学会学術集会
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[Presentation] A Phase 2b study of an oral HDAC inhibitor HBI-8000 in patients with relapsed or refractory PTCL2021
Author(s)
Hidetsugu Kawai, Jun Ando, Ilseung Choi, Junya Kuroda, Mitsutoshi Kurosawa, Hong Ghi Lee, Jae Hoon Lee, Won Sik Lee, Hironobu Minami, Hirokazu Nagai, Hirohiko Shibayama, Takeo Shindo, Kenji Tsukamoto, Kunihiro Tsukasaki, Toshiki Uchida, Shinya Rai, Deok Hwan Yang, Shinichiro Yoshida, Mireille Gillings, Kensei Tobinai
Organizer
第83回日本血液学会学術集会
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[Presentation] Genetic features of AML requiring hematopoietic stem cell transplantation: HM-SCREEN-JAPAN012021
Author(s)
Motoki Eguchi, Takanobu Morishita, SunGi Chi, Kentaro Fukushima, Hirohiko Shibayama, Naoko Hosono, Takahiro Yamauchi, Seiichiro Katagiri, Akihiko Gotoh, Naoto Takahashi, Satoshi Iyama, Makoto Nakamura, Yukinobu Nakamura, Suguru Fukuhara, Koji Izutsu, Hirohiko Yamauchi, Junichiro Yuda, Yosuke Minami
Organizer
第83回日本血液学会学術集会
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[Presentation] Clinical significance of FLT3 mutations in a NGS multicenter study of AML: HM-SCREEN-JAPAN012021
Author(s)
Kentaro Fukushima, Hirohiko Shibayama, SunGi Chi, Nohoko Hosono, Takahiro Yamauchi, Seiichiro Katagiri, Akihiko Gotoh, Naoto Takahashi, Satoshi Iyama, Makoto Nakamura, Yukinobu Nakamura, Suguru Fukuhara, Koji Izutsu, Hirohiko Yamauchi, Junichiro Yuda, Yosuke Minami
Organizer
第83回日本血液学会学術集会
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[Presentation] ASXL1 Mutations Predict a Poor Response to Darbepoetin Alfa in Anemic Patients with Low-Risk MDS: A Multicenter, Phase II Study.2020
Author(s)
Hitoshi Hanamoto, Yasuyoshi Morita, Motoshi Ichikawa, Yasuhito Nannya, Hirohiko Shibayama, Yoshinobu Maeda, Tomoko Hata, Toshihiro Miyamoto, Hiroshi Kawabata, Kazuto Takeuchi, Hiroko Tanaka, Junji Kishimoto, Satoru Miyano, Itaru Matsumura, Seishi Ogawa, Koichi Akashi, Yuzuru Kanakura, Kinuko Mitani
Organizer
The American Society of Hematology 62nd Annual Meeting
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Int'l Joint Research
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[Presentation] The Phase 3 TOURMALINE-MM2 Trial: Oral Ixazomib, Lenalidomide, and Dexamethasone (IRd) Vs Placebo-Rd for Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma (NDMM).2020
Author(s)
Thierry Facon, Christopher P. Nizar Bahlis, Fritz Offner, Darrell J White, Lotfi Benboubker, Sophie Rigaudeau, Philippe Rodon, Sung-Soo Yoon, Kenshi Suzuki, Hirohiko Shibayama, Xiaoquan Zhang, Godwin Yung, Robert M. Rifkin, Philippe Moreau, Sagar Lonial, Shaji K. Kumar, Paul G. Richardson, Vincent Rajkumar
Organizer
The American Society of Hematology 62nd Annual Meeting
Related Report
Int'l Joint Research
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[Presentation] ASXL1 mutations predict a poor response to darbepoetin alfa in anemic patients with low-risk MDS2020
Author(s)
Hirohiko Shibayama, Yasuyoshi Morita, Motoshi Ichikawa, Yasuhito Nannya, Hitoshi Hanamoto, Yoshinobu Maeda, Tomoko Hata, Toshihiro Miyamoto, Hiroshi Kawabata,Kazuto Takeuchi,Hiroko Tanaka,Junji Kishimoto,Satoru Miyano,Itaru Matsumura,Seishi Ogawa, Koichi Akashi, Yuzuru Kanakura, Kinuko Mitani
Organizer
第82回日本血液学会学術集会
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[Presentation] ENTEROCOCCUS-PREDOMINANT INTESTINAL MICROBIOTA INDICATES POOR PROGNOSIS AFTER HEMATOPOIETIC STEM CELL TRANSPLANTATION.2019
Author(s)
Shinsuke Kusakabe, Kentaro Fukushima, Takafumi Yokota, Ritsuko Nakai, Akihisa Hino, Yasuhiro Nagate, Yukiko Doi, Jiro Fujita, Daisuke Motooka, Shota Nakamura, Hirohiko Shibayama, Yuzuru Kanakura
Organizer
The 24th European Hematology Association
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Int'l Joint Research
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[Presentation] The influence of tumor immune microenvironment and tumor immunity on the pathogenesis, treatment and prognosis of post-transplant lymphoproliferative disorders (PTLD).2019
Author(s)
Hideaki Saito, Hirohiko Shibayama, Hiroaki Miyoshi, Jun Toda, Shinsuke Kusakabe, Michiko Ichii, Jiro Fujita, Kentaro Fukushima, Takafumi Yokota, Tetsuo Maeda, Maso Mizuki, Kenji Oritani, Masao Seto, Koichi Ohshima, Yuzuru Kanakura
Organizer
15th International Conference on Malignant Lymphoma
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Int'l Joint Research
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[Presentation] Elevated serum soluble interleukin-2 receptor level is a useful prognostic factor for disease-specific overall survival in patients with newly diagnosed follicular lymphoma before initiation of treatment.2019
Author(s)
Nozaki K, Sugahara H, Ueda S, Ishikawa J, Fuji S, Masaie H, Tada Y, Suga M, Tsutsumi K, Shibata K, Kida S, Karasuno, T Sata H, Yasumi,5 Masato Iida M, Mitsui H,Kamae T, Saito, N Murakami H, Moriyama Y, Kawakami M,Kato R, Nakae Y,Kida T, Kosugi S, Nakagawa, M Uchida Y, Azenishi Y, Sakaniwa R, Kitamura T, Shibayama H
Organizer
The American Society of Hematology 61th Annual Meeting
Related Report
Int'l Joint Research
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[Presentation] Phase 2 Study of Tirabrutinib (ONO/GS-4059), a Second-Generation Bruton’s Tyrosine Kinase Inhibitor, Monotherapy in Patients with Treatment-Naive or Relapsed/Refractory Waldenstrom Macroglobulinemia.2019
Author(s)
Wataru Munakata, Naohiro Sekiguchi, Rai Shinya, Kenshi Suzuki, Hiroshi Handa, Hirohiko Shibayama, Tomoyuki Endo, Yasuhito Terui, Noriko Iwaki, Noriko Fukuhara, Hiro Tatetsu, Shinsuke Iida, Takayuki Ishikawa, Ryota Shiibashi, Koji Izutsu
Organizer
The American Society of Hematology 61th Annual Meeting
Related Report
Int'l Joint Research
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[Presentation] A young male immunocompetent patient of atypical CD56- EBER1- extraosseous plasmacytoma with plasmablastic morphology.2019
Author(s)
Nakai R, Ueda Y, Wada N, Hino A, Kusakabe S, Nagate Y, Doi Y, Fujita J, Fukushima K, Yokota T, Shibayama H, Morii E, Kanakura Y.
Organizer
第59回 リンパ網内系学会
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[Presentation] Contributions of high number of PD-1+ tumor infiltrating lymphocytes to early onset of PTLD.2019
Author(s)
Hideaki Saito, Hiroaki Miyoshi, Hirohiko Shibayama, Jun Toda, Shinsuke Kusakabe, Michiko Ichii, Jiro Fujita, Kentaro Fukushima, Tetsuo Maeda, Masao Mizuki, Kenji Oritani, Masao Seto, Takafumi Yokota, Yuzuru Kanakura, and Koichi Ohshima
Organizer
第81回日本血液学会学術集会
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[Presentation] 抗CD38 抗体isatuximab単剤による日本人の再発難治多発性骨髄腫患者を対象とした第1/2相試験2019
Author(s)
李 政樹, 角南一貴, 松本守生, 島崎千尋, 麻奥英毅, 丸山 大, 柴山浩彦, 石澤 賢一, 高松博幸, 池田宇次, 金子仁臣, 内山倫宏, 木口 亨, 井山 諭, 村上博和, 佐々木 亨, 多田圭佑, 鈴木憲史, 飯田真介
Organizer
第81回日本血液学会学術集会
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[Presentation] 実臨床におけるイキサゾミブの治療成績:関西ミエローマフォーラムのデータベースによる多施設後方視的解析2019
Author(s)
高桑輝人, 山村亮介, 太田健介, 金子仁臣, 今田和典, 中谷 綾, 淵田真一, 柴山浩彦, 松田光弘, 島津 裕, 足立陽子, 小杉 智, 内山人二, 田中宏和, 花本 仁, 志村勇司, 諫田淳也, 恩田佳幸, 魚嶋伸彦, 八木秀男, 吉原 哲, 日野雅之, 島崎千尋, 高折晃史, 黒田純也, 松村 到, 金倉 譲, 野村昌作
Organizer
第81回日本血液学会学術集会
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[Presentation] 多発性骨髄腫におけるクリニカルシークエンスの実行可能性の研究2019
Author(s)
李 政樹, 安田貴彦, 半田 寛, 石田禎夫, 柴山浩彦, 安倍正博, 金森貴之, 真田 昌, 服部浩佳, 西島 大, 倉橋浩樹, 白石友一, 山本松雄, 齋藤明子, 宮野 悟, 小川誠司, 堀部敬三, 飯田真介
Organizer
第81回日本血液学会学術集会
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