Clarification of the roles of anamorsin in the lymphocytes differentiation and proliferation
Project/Area Number |
16K09871
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Hematology
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Research Institution | Osaka University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
金倉 譲 大阪大学, 医学系研究科, 教授 (20177489)
織谷 健司 大阪大学, 医学系研究科, 准教授 (70324762)
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | アナモルシン / 鉄・硫黄クラスター / 遺伝子改変マウス / Bリンパ球 / P38MAPK / コンディショナルノックアウトマウス / Tリンパ球 / アポトーシス / p38MAPK / B リンパ球 / T リンパ球 / 免疫学 / リンパ球 / 鉄硫黄クラスター蛋白 |
Outline of Final Research Achievements |
Anamorsin (AM), an anti-apoptotic molecule, which we have identified was revealed to be the molecule that works related to iron-sulfur (Fe-S) proteins biosynthesis. In order to clarify the functions of AM in the various cells in vivo and the Fe-S cluster proteins which play important roles in those cells, we produced the AM conditional knock out mice (AM Flox/Flox mice). In this study, we mated CD19 Cre Tg mice with AM Flox/Flox mice to produce B lymphocytes specific AM deficient mice, and analyzed the phenotypes of these mice. We found that the number of the terminal differentiated B lymphocytes (FOLI cells) was markedly decreased in those mice. Furthermore, we found that the expression of P38MAPK was remarkably decreased in both mRNA and protein levels in the AM deficient FOLI cells. From those results, it was shown that AM regulates the expression of P38MAPK in the terminal differentiated B lymphocytes (FOLI cells).
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Academic Significance and Societal Importance of the Research Achievements |
鉄・硫黄(Fe-S)クラスター分子の形成にアナモルシン(AM)は必須の分子である。興味深いことに細胞種ごとでAMが関連するFe-Sクラスター分子は異なっており、それらを明らかにすることは、AMを標的とした薬剤の開発に寄与すると考えられる。本研究では、遺伝子改変マウスを用いることでBリンパ球の分化・増殖においては、AMはP38MAPKの発現に強く関わっていることが明らかとなった。P38MAPKはシグナル伝達分子の一つだが、AMが欠損すると、その発現が低下し、Bリンパ球の分化が停止することが明らかとなったことで、AMを標的とした薬剤でBリンパ球の分化を制御できる可能性が示された。
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Report
(4 results)
Research Products
(21 results)
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[Journal Article] Variable SATB1 Levels Regulate Hematopoietic Stem Cell Heterogeneity with Distinct Lineage Fate2018
Author(s)
Yukiko Doi, Takafumi Yokota, Yusuke Satoh, Daisuke Okuzaki, Masahiro Tokunaga, Tomohiko Ishibashi, Takao Sudo, Tomoaki Ueda, Yasuhiro Shingai, Michiko Ichii, Akira Tanimura, Sachiko Ezoe, Hirohiko Shibayama, Terumi Kohwi-Shigematsu, Junji Takeda, Kenji Oritani, and Yuzuru Kanakura
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Journal Title
Cell Reports
Volume: 23
Issue: 11
Pages: 3223-3235
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Retrospective analysis of primary plasma cell leukemia in Kansai Myeloma Forum registry2018
Author(s)
Nakaya A, Yagi H, Kaneko H, Kosugi S, Kida T, Adachi Y, Shibayama H, Kohara T, Kamitsuji Y, Fuchida SI, Uoshima N, Kawata E, Uchiyama H, Shimura Y, Takahashi T, Urase F, Ohta K, Hamada T, Miyamoto K, Kobayashi M, Shindo M, Tanaka H, Shimazaki C, Hino M, Kuroda J, Kanakura Y, Takaoari-Kondo A, Nomura S, Matsumura I
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Journal Title
Leukemia Research Reports
Volume: 10
Pages: 7-10
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Identification of MS4A3 as a reliable marker for early myeloid differentiation in human hematopoiesis.2018
Author(s)
Ishibashi T, Yokota T, Satoh Y, Ichii M, Sudo T, Doi Y, Ueda T, Nagate Y, Hamanaka Y, Tanimura A, Ezoe S, Shibayama H, Oritani K, Kanakura Y.
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Journal Title
Biochemical and Biophysical Research Communications
Volume: 495
Issue: 3
Pages: 2338-2343
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Pomalidomide with or without dexamethasone for relapsed/refractory multiple myeloma in Japan: a retrospective analysis by the Kansai Myeloma Forum2018
Author(s)
Matsumura-Kimoto Y, Kuroda J, Kaneko H, Kamitsuji Y, Fuchida SI, Nakaya A, Shibayama H, Uoshima N, Yokota I, Uchiyama H, Yagi H, Kosugi S, Matsui T, Ishikawa J, Matsuda M, Ohta K, Iida M, Tanaka H, Kobayashi M, Wada K, Shimazaki C, Nomura S, Imada K, Hino M, Matsumura I, Kanakura Y, Takaori-Kondo A; KMF
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Journal Title
International Journal of Hematology
Volume: 107
Issue: 5
Pages: 541-550
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Distinct effects of daratumumab on indirect and direct antiglobulin tests: a new method employing 0.01 mol/L dithiothreitol for negating the daratumumab interference with preserving K antigenicity (Osaka method).2018
Author(s)
Hosokawa M, Kashiwagi H, Nakayama K, Sakuragi M, Nakao M, Morikawa T, Kiyokawa T, Aochi H, Nagamine K, Shibayama H, Tomiyama Y.
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Journal Title
Transfusion
Volume: 58
Issue: 12
Pages: 3003-3013
DOI
Related Report
Peer Reviewed
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[Presentation] Brentuximab vedotin plus chemotherapy in high-risk, advanced-stage classical Hodgkin lymphoma patients: Results of pre-specified sub-group analyses from the ECHELON-1 study.2018
Author(s)
Martin Hutchings, John Radford, Andrea Gallamini, Arpad Illes, Anna Sureda, Joseph M. Connors, Alice Sykorova, Hirohiko Shibayama, Jeremy S. Abramson, Neil Chua, Jonathan W. Friedberg, Jan Koren, Ann Steward LaCasce, Lysiane Molina, Neil Josephson, Eric Song, Hina Jolin, Rachael Liu, Ashish Gautam, Stephen Ansell
Organizer
23rd Congress of the European Hematology Association
Related Report
Int'l Joint Research
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[Presentation] Ectonucleosidase CD39 Is Highly Expressed on ATLL Cells and Suppresses the Immune Response through theAdenosine Pathway.2018
Author(s)
Yasuhiro Nagate, Sachiko Ezoe, Jiro Fujita, Takafumi Yokota, Michiko Ichii, Akira Tanimura, Yukiko Doi, Tomoaki Ueda, Jun Toda, Hirohiko Shibayama, Kenji Oritani, Yuzuru Kanakura
Organizer
The American Society of Hematology 60th Annual Meeting
Related Report
Int'l Joint Research
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[Presentation] A Novel Unifrac-Based Analytical Method for Determining Sequential Changes in Gut Microbiota after Hematopoietic Stem Cell Transplantation.2018
Author(s)
Shinsuke Kusakabe, Kentaro Fukushima, Tetsuo Maeda, Takafumi Yokota, Ritsuko Nakai, Akihisa Hino, Yasuhiro Nagate, Jiro Fujita, Motooka Daisuke, Shota Nakamura, Hirohiko Shibayama, Yuzuru Kanakura
Organizer
The American Society of Hematology 60th Annual Meeting
Related Report
Int'l Joint Research
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[Presentation] ESAM on the Cells of Endothelial Lineage Plays an Important Role in the Development of Definitive Hematopoiesis.2018
Author(s)
Tomoaki Ueda, Takafumi Yokota, Yoshihiro Uno, Tomoji Mashimo, Takao Sudo, Tomohiko Ishibashi, Yukiko Doi1, Yasuhiro Shingai, Akira Tanimura, Michiko Ichii, Sachiko Ezoe, Hirohiko Shibayama, Kenji Oritani, Yuzuru Kanakura
Organizer
The American Society of Hematology 60th Annual Meeting
Related Report
Int'l Joint Research
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[Presentation] Signal Transducing Adaptor Protein (STAP) Family Accelerates Gut and Thymic Graft-Versus-Host-Disease in Murine Model.2018
Author(s)
Hideaki Saito, Michiko Ichii, Jun Toda, Yuichi Kitai, Ryuta Muromoto, Jun-ichi Kashiwakura, Kodai Saitoh, Hirohiko Shibayama, Tadashi Matsuda, Kenji Oritani, Yuzuru Kanakura
Organizer
The American Society of Hematology 60th Annual Meeting
Related Report
Int'l Joint Research
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[Presentation] Anamorsin plays important roles in B-cell development2016
Author(s)
濱中有理, 柴山浩彦, 谷村朗, 横田貴史, 江副幸子, 一井倫子, 石橋知彦, 土居由貴子, 長手泰宏, 織谷健司, 金倉譲
Organizer
第78回日本血液学会学術集会
Place of Presentation
パシフィコ横浜, 神奈川
Year and Date
2016-10-14
Related Report
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[Presentation] Anamorsin is essential for B-cell terminal differentiation.2016
Author(s)
Hamanaka Y, Shibayama H, Tanimura A, Yokota T, Ezoe S, Ichii M, Ishibashi T, Doi Y, Nagate Y, Oritani K, Kanakura Y
Organizer
21st Congress of European Hematology Association
Place of Presentation
The Bella Center, Copenhagen, Denmark
Year and Date
2016-06-11
Related Report
Int'l Joint Research