Analysis of the functions of anti-apoptotic molecule, Anamorsin -the roles in hematopoiesis and cellular iron metabolism-

• Project/Area Number: 25293220
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Osaka University
• Principal Investigator: KANAKURA Yuzuru 大阪大学, 医学(系)研究科(研究院), 教授 (20177489)
• Co-Investigator(Kenkyū-buntansha): SHIBAYAMA Hirohiko 大阪大学, 大学院医学系研究科, 講師 (60346202) ; ORITANI Kenji 大阪大学, 大学院医学系研究科, 准教授 (70324762) ; MIZUKI Masao 大阪大学, 医学部附属病院, 准教授 (80283761)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000); Fiscal Year 2015: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2014: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2013: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
• Keywords: アナモルシン / コンディショナルノックアウトマウス / 造血幹細胞 / 鉄・硫黄クラスター / アポトーシス / 鉄硫黄クラスター蛋白 / 遺伝子改変マウス / 鉄代謝 / 骨髄異形成症候群 / 細胞内鉄代謝

Outline of Final Research Achievements

In this study, we have generated Anamorsin (AM) conditional knock-out mice, which delete AM in the specific organ by mating the organ-specific Cre recombinase transgenic mice, and analyzed the functions of AM in the specific organ. The defect of AM in the embryonic hematopoietic stem cells leads to anemia and embryonic lethality, which are identical with the phenotypes of AM deficient mice. The induction of AM deficiency in the hematopoietic cells in the adult mice lead to the increase of apoptosis in the hematopoietic stem cells. From these data, it was shown that AM plays important roles in both of the embryonic and adult hematopoietic stem cells.

Research Products

• [Journal Article] Estrogen-inducible sFRP5 inhibits early B-lymphopoiesis in vivo, but not during pregnancy (2015)
  • Author(s): Takafumi Yokota, Kenji Oritani, Takao Sudo, Tomohiko Ishibashi1, Yukiko Doi, Yoko Habuchi, Michiko Ichii, Kentaro Fukushima, Daisuke Okuzaki, Kazuma Tomizuka, Kengo Yamawaki, Makoto Kakitani, Akihiko Shimono, Eiichi Morii, Paul W. Kincade, Yuzuru Kanakura
  • Journal Title: European Journal of Immunology Volume: in press Issue: 5 Pages: 1390-1401
  • DOI: 10.1002/eji.201444939
  • Peer Reviewed / Open Access
• [Journal Article] Identification of osteoblast stimulating factor 5 as a negative regulator in the B-lymphopoietic niche. (2015)
  • Author(s): Fujita N, Ichii M, Maeda T, Saitoh N, Yokota T, Yamawaki K, Kakitani M, Tomizuka K, Oritani K, Kanakura Y
  • Journal Title: Experimental Hematology Volume: 43 Issue: 11 Pages: 963-973
  • DOI: 10.1016/j.exphem.2015.07.002
  • Peer Reviewed
• [Journal Article] A new diagnostic kit, ODK-1201, for the quantitation of low major BCR-ABL mRNA level in chronic myeloid leukemia: correlation of quantitation with major BCR-ABL mRNA kits. (2015)
  • Author(s): Nakamae H, Matsumura I, Naoe T,et al.
  • Journal Title: Int J Hematol. Volume: 102 Issue: 3 Pages: 301-311
  • DOI: 10.1007/s12185-015-1826-9
  • Peer Reviewed / Open Access
• [Journal Article] Quantitative polymerase chain reaction analysis with allele-specific oligonucleotide primers for individual IgH VDJ regions to evaluate tumor burden in myeloma patients. (2015)
  • Author(s): Sata H, Shibayama H, Maeda I, Habuchi Y, Nakatani E, Fukushima K, Fujita J, Ezoe S, Tadokoro S, Maeda T, Mizuki M, Kosugi S, Nakagawa M, Ueda S, Iida M, Tokumine Y, Azenishi Y, Mitsui H, Oritani K, Kanakura Y.
  • Journal Title: Exp Hematol. Volume: 印刷中 Issue: 5 Pages: 374-381
  • DOI: 10.1016/j.exphem.2015.01.002
  • Peer Reviewed
• [Journal Article] The preventative effects of recombinant thrombomodulin on transplantation- associated coagulopathy after allogeneic hematopoietic stem cell transplantation (2014)
  • Author(s): Nomura S, Ishii K, Maeda Y, Katayama Y, Yagi H, Fujishima N, Ota S, Seki M, Okada M, Ikezoe T, Hayashi K, Fujita S, Satake A, Ito T, Kyo T, Ishida Y, Chiba S, Ogawa H, Tanimoto M, Sawada K
  • Journal Title: Journal of Stem Cell Research & Therapy Volume: 4 Issue: 1 Pages: 247-247
  • DOI: 10.1007/s12185-014-1696-6
  • Peer Reviewed / Open Access
• [Journal Article] The anti-apoptotic gene Anamorsin is essential for both autonomous and extrinsic regulation of murine fetal liver hematopoiesis. (2014)
  • Author(s): Tanimura A, Shibayama H, Hamanaka Y, Fujita N, Ishibashi T, Sudo T, Yokota T, Ezoe S, Tanaka H, Matsumura I, Oritani K, Kanakura Y.
  • Journal Title: Exp Hematol. Volume: 42 Issue: 5 Pages: 410-422
  • DOI: 10.1016/j.exphem.2014.01.002
  • Peer Reviewed / Open Access
• [Journal Article] Anamorsin, a novel caspase-3 substrate in neurodegeneration. (2014)
  • Author(s): Yun N, Lee YM, Kim C, Shibayama H, Tanimura A, Hamanaka Y, Kanakura Y, Park IS, Jo A, Shin JH, Ju C, Kim WK, Oh YJ.
  • Journal Title: J Biol Chem Volume: 289 Issue: 32 Pages: 22183-22195
  • DOI: 10.1074/jbc.m114.552679
  • Peer Reviewed
• [Journal Article] Long-term efficacy and safety of eculizumab in Japanese patients with PNH: AEGIS trial. (2013)
  • Author(s): Kanakura Y, Ohyashiki K, Shichishima T, Okamoto S, Ando K, Ninomiya H, Kawaguchi T, Nakao S, Nakakuma H, Nishimura J, Kinoshita T, Bedrosian CL, Ozawa K, Omine M.
  • Journal Title: Int J Hematol Volume: 98 Issue: 4 Pages: 406-416
  • DOI: 10.1007/s12185-013-1404-y
  • Peer Reviewed
• [Journal Article] The Satb1 protein directs hematopoietic stem cell differentiation toward lymphoid lineages. (2013)
  • Author(s): Satoh Y, Yokota T, Sudo T, Kondo M, Lai A, Kincade PW, Kouro T, Iida R, Kokame K, Miyata T, Habuchi Y, Matsui K, Tanaka H, Matsumura I, Oritani K, Kohwi-Shigematsu T, Kanakura Y.
  • Journal Title: Immunity Volume: 38 Issue: 6 Pages: 1105-1115
  • DOI: 10.1016/j.immuni.2013.05.014
  • Peer Reviewed
• [Journal Article] Clinical evaluation of WT1 mRNA expression levels in peripheral blood and bone marrow in patients with myelodysplastic syndromes. (2013)
  • Author(s): Ueda Y
  • Journal Title: Leukemia & Lymphoma Volume: 未定 Issue: 7 Pages: 1450-1458
  • DOI: 10.3109/10428194.2012.745074
  • Peer Reviewed
• [Presentation] SATB1 expression marks lymphoid-lineage-biased hematopoietic stem cells in mouse bone marrow. (2015)
  • Author(s): Doi Y, Yokota T, Ishibashi1 T, Satoh Y, Ichii M, Tanimura A, Ezoe S, Shibayama H, Oritani K, Kanakura Y.
  • Organizer: The American Society of Hematology 57th Annual Meeting
  • Place of Presentation: Orange County Convention Center, Orland, FL, USA
  • Year and Date: 2015-12-06
  • Int'l Joint Research
• [Presentation] Second primary malignancies among patients with myeloma-related-diseases in KMF database. (2015)
  • Author(s): 小杉智, 柴山浩彦, 中谷英仁, 太田健介, 金子仁臣, 八木秀男, 田中宏和, 淵田真一, 中谷綾, 小林正行, 黒田純也 , 島崎千尋, 野村昌作, 日野雅之, 松村到, 谷脇雅史, 金倉譲, 高折晃史
  • Organizer: 第77回日本血液学会学術集会
  • Place of Presentation: ホテル日航金沢，石川県金沢市
  • Year and Date: 2015-10-18
• [Presentation] Retrospective analysis of MM patients with dual refractory to bortezomib and IMiDs in KMF registry. (2015)
  • Author(s): 小原尚恵, 柴山浩彦, 中谷英仁, 金子仁臣, 淵田真一, 八木秀男, 黒田純也, 小林正行, 野村昌作, 島崎千尋, 通堂満, 日野雅之, 松村到, 谷脇雅史, 金倉譲, 高折晃史
  • Organizer: 第77回日本血液学会学術集会
  • Place of Presentation: ホテル日航金沢，石川県金沢市
  • Year and Date: 2015-10-17
• [Presentation] Endothelial cell-selective adhesion molecule is a novel human hematopoietic stem cell markerassociated with a subset of human leukemias. (2015)
  • Author(s): Ishibashi T,Yokota T, Tanaka H, Ichii1 M, Sudo T, Satoh Y, Doi Y, Tanimura A, Hamanaka Y, Ezoe S, Shibayama H, Oritani K, Kanakura Y.
  • Organizer: The 44th Annual Scientific Meeting of International Society of Exoerimental Hematology (ISEH)
  • Place of Presentation: Kyoto International Conference Center, Kyoto, Japan
  • Year and Date: 2015-09-18
  • Int'l Joint Research
• [Presentation] An Anti-Apoptotic Molecule, Anamorsin, Is Upregulated in Anemia and Essential for Imperative Erythropoiesis. (2015)
  • Author(s): Akira Tanimura, Hirohiko Shibayama, Yuri Hamanaka, Natsuko Fujita, Yasuhiro Nagate, Tomohiko Ishibashi, Michiko Ichii, Takafumi Yokota, Sachiko Ezoe, Kenji Oritani, and Yuzuru Kanakura
  • Organizer: 第6回 JSH International Symposium 2015
  • Place of Presentation: 軽井沢プリンスホテル, 長野県北佐久郡
  • Year and Date: 2015-05-23
  • Int'l Joint Research
• [Presentation] An anti-apoptotic molecule, Anamorsin, is upregulated in anemia and essential for imperative erythropoiesis (2014)
  • Author(s): Tanimura A, Shibayama H, Hamanaka Y, Fujita N, Nagate Y, Ishibashi T, Saitoh N, Ichii M, Yokota T, Ezoe S, Oritani K, Kanakura Y
  • Organizer: The American Society of Hematology 56th Annual Meeting
  • Place of Presentation: Moscone Center, San Francisco, CA, USA
  • Year and Date: 2014-12-08
• [Presentation] Anamorsin overexpression leads to dysregulation of lipopolysaccharide-stimulated B cell proliferation through Ras signaling (2014)
  • Author(s): Hamanaka Y, Shibayama H, Tanimura A, Yokota T, Ezoe S, Saito N, Ichii M, Matsui K, Sudo T, Ishibashi T, Doi Y, Nagate Y, Takemoto M, Oritani K, Kanakura Y
  • Organizer: The American Society of Hematology 56th Annual Meeting
  • Place of Presentation: Moscone Center, San Francisco, CA, USA
  • Year and Date: 2014-12-08
• [Presentation] アナモルシントランスジェニックマウスを用いたアナモルシンの機能解析 (2014)
  • Author(s): 濱中有理，柴山浩彦，谷村 朗，横田貴史，江副幸子，齊藤則充，一井倫子，松井敬子，数藤孝雄，石橋知彦，土居由貴子，長手泰宏，竹本雅子，織谷健司，金倉 譲
  • Organizer: 第76回日本血液学会学術集会
  • Place of Presentation: 大阪国際会議場, 大阪
  • Year and Date: 2014-11-02
• [Presentation] Succession of tradition and challenges towards the future: a personal view (2014)
  • Author(s): 金倉譲
  • Organizer: 第76回日本血液学会学術集会
  • Place of Presentation: 大阪国際会議場, 大阪
  • Year and Date: 2014-10-31
  • Invited
• [Presentation] An anti-apoptotic molecule, Anamorsin, is upregulated in anemia and essential for erythropoiesis (2014)
  • Author(s): Tanimura A, Hamanaka Y, Fujita N, Nagate Y, Ishibashi T, Matsui K, Saitoh N, Ichii M, Ezoe S, Yokota T, Oritani K, Shibayama H, Kanakura Y
  • Organizer: 第76回日本血液学会学術集会
  • Place of Presentation: 大阪国際会議場, 大阪
  • Year and Date: 2014-10-31
• [Presentation] Analysis of human endosteal HSC niche; a novel CD34high ESAMhigh subset is adjacent to trabecular areas of human bone marrow (2013)
  • Author(s): Ichii M, Oritani K, Yokota T, Ishibashi T, Sudo T, Fujita N, Kincade PW, Kanakura Y
  • Organizer: The 18th Congress of European Hematology Association
  • Place of Presentation: Stockholm International Fairs & Congress Center, Stockholm, Sweden
• [Presentation] A Rare Genetic Polymorphism In C5 Confers Poor Response To The Anti-C5 Monoclonal Antibody Eculizumab In 11 Japanese Patients With PNH (2013)
  • Author(s): Nishimura J, Yamamoto M, Hayashi S, Ohyashiki K, Ando K, Noji H, Kitamura K, Eto T, Takahashi T, Masuko M, Matsumoto T, Wano Y, Shichishima T, Shibayama H, Hase M, Lan L, Johnson K, Tamburini P, Inazawa J, Kinoshita T, Kanakura Y
  • Organizer: The American Society of Hematology 55th Annual Meeting
  • Place of Presentation: Ernest N. Morial Convention Center, New Orleans, LA, USA
• [Presentation] Endothelial Cell-Selective Adhesion Molecule Marks Human Hematopoietic Stem Cells Regardless Of The HSC Sources (2013)
  • Author(s): Ishibashi T, Yokota T, Ichii M, Satoh Y, Sudo T, Doi Y, Fujita N, Nagate Y, Hamanaka Y, Matsui K, Tanimura A, Saitoh N, Ezoe S, Shibayama H, Kincade PW, Oritani1 K, Kanakura Y
  • Organizer: The American Society of Hematology 55th Annual Meeting
  • Place of Presentation: Ernest N. Morial Convention Center, New Orleans, LA, USA
• [Presentation] SFRP5 inhibits early B-lymphopoiesis and modulates estrogen-induced changes in the immune system (2013)
  • Author(s): Yokota T, Oritani K, Sudo T, Ishibashi T, Doi Y, Ichii M, Tomizuka K, Yamawaki K, Shimono A, Kanakura Y
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: ロイトン札幌・さっぽろ芸文館・札幌市教育文化会館, 北海道
• [Presentation] MS4A3発現はヒト造血における早期骨髄球系分化の指標となる (2013)
  • Author(s): 石橋知彦, 横田貴史, 佐藤友亮, 数藤孝雄, 一井倫子, 柴山浩彦, 江副幸子, 谷村 朗, 藤田奈津子, 松井敬子, 濱中有理, 土居由貴子, 織谷健司, 金倉 譲
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: ロイトン札幌・さっぽろ芸文館・札幌市教育文化会館, 北海道
• [Remarks] 大阪大学大学院医学系研究科 血液・腫瘍内科ホームページ
• [Remarks] 大阪大学大学院医学系研究科 血液・腫瘍内科 ホームページ