Analysis of functions of anamorsin, an anti-apoptotic molecule, in hematopoiesis

2012 Fiscal Year Final Research Report

• Project/Area Number: 22390194
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Osaka University
• Principal Investigator: KANAKURA Yuzuru 大阪大学, 医学系研究科, 教授 (20177489)
• Co-Investigator(Kenkyū-buntansha): ORITANI Kenji 大阪大学, 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) ; SHIBAYAMA Hirohiko 大阪大学, 医学系研究科, 講師 (60346202)
• Project Period (FY): 2010 – 2012
• Keywords: アナモルシン / 遺伝子改変マウス / 造血 / 鉄・硫黄クラスター / ROS / アポトーシス

Research Abstract

We clarified anamorsin (AM) played important roles on definitive hematopoiesis in both of hematopoietic stem cells and fetal liver stromal cells by using AM deficient fetal liver. Furthermore, we found AM deficiency impaired the iron homeostasis through iron/sulfur protein biogenesis and resulted in the increase of labile iron pool, the accumulation of ROS and the induction of apoptosis.

Research Products

• [Journal Article] C-terminal mutation of RUNX1 attenuates the DNA-damage repair response in hematopoietic stem cells (2012)
  • Author(s): Satoh Y, Matsumura I, Tanaka H, Harada H, Harada Y, Matsui K, Shibata M, Mizuki M, Kanakura Y
  • Journal Title: Leukemia Volume: 26 Pages: 303-311
  • Peer Reviewed
• [Journal Article] NAD-dependent histone deacetylase, SIRT1, plays essential roles in the maintenance of hematopoietic stem cells (2012)
  • Author(s): Matsui K, Ezoe S, Oritani K, Shibata M, Tokunaga M, Fujita N, Tanimura A, Sudo T, Tanaka H, McBurney MW, Matsumura I, Kanakura Y
  • Journal Title: Biochem Biophys Res Commun Volume: 418 Pages: 811-817
  • Peer Reviewed
• [Journal Article] Recognition of highly restricted regions in the β-propeller domain of αIIb by platelet-associated anti-αIIbβ3 autoantibodies in primary immune thrombocytopenia. (2012)
  • Author(s): Kiyomizu K, Kashiwagi H, Nakazawa T, Tadokoro S, Honda S, Kanakura Y, Tomiyama Y
  • Journal Title: Blood Volume: 120 Pages: 1499-1509
  • Peer Reviewed
• [Journal Article] The endothelial antigen ESAM monitors hematopoietic stem cell status between quiescence and self-renewal (2012)
  • Author(s): Sudo T, Yokota T, Oritani K, Satoh Y, Sugiyama T, Ishida T, Shibayama H, Ezoe S, Fujita N, Tanaka H, Maeda T, Nagasawa T, Kanakura Y
  • Journal Title: J Immunol Volume: 189 Pages: 200-210
  • Peer Reviewed
• [Journal Article] Effect of vasodilators in patient with pulmonary hypertension associated with hemolytic anemia (2012)
  • Author(s): Yoshida A, Mizote I, Sakata Y, Maeda T, Kanakura Y, Yamauchi-Takihara K, Komuro I
  • Journal Title: J Cardiol Cases Volume: 6 Pages: e75-e77
  • Peer Reviewed
• [Journal Article] Deregulated expression of HMGA2 is implicated in clonal expansion of PIGA deficient cells in paroxysmal nocturnal haemoglobinuria (2012)
  • Author(s): Murakami Y, Inoue N, Shichishima T, Ohta R, Noji H, Maeda Y, Nishimura JI, Kanakura Y, Kinoshita T
  • Journal Title: Br J Haematol Volume: 156 Pages: 383-387
  • Peer Reviewed
• [Journal Article] Safety and efficacy of the terminal complement inhibitor eculizumab in Japanese patients with paroxysmal nocturnal hemoglobinuria: the AEGIS Clinical Trial (2011)
  • 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, Valentine ME, Khursigara G, Ozawa K, Omine M
  • Journal Title: Int J Hematol Volume: 93 Pages: 36-46
  • Peer Reviewed
• [Journal Article] A potential role for α-actinin in inside-out αIIbβ3 signaling. (2011)
  • Author(s): Tadokoro S, Nakazawa T, Kamae T, Kiyomizu K, Kashiwagi H, Honda S, Kanakura Y, Tomiyama Y
  • Journal Title: Blood Volume: 117 Pages: 250-258
  • Peer Reviewed
• [Journal Article] Identification of functional domains and novel binding partners of STIM proteins (2011)
  • Author(s): Saitoh N, Oritani K, Saito K, Yokota T, Ichii M, Sudo T, Fujita N, Nakajima K, Okada M, Kanakura Y
  • Journal Title: J Cell Biochem Volume: 112 Pages: 147-156
  • Peer Reviewed
• [Journal Article] Predictability of the response to tyrosine kinase inhibitors via in vitro analysis of Bcr-Abl phosphorylation (2011)
  • Author(s): Shibata M, Ezoe S, Oritani K, Matsui K, Tokunaga M, Fujita N, Saito Y, Takahashi T, Hino M, Matsumura I, Kanakura Y
  • Journal Title: Leuk Res Volume: 35 Pages: 1205-1211
  • Peer Reviewed
• [Journal Article] Myeloid neoplasm-related gene abnormalities differentially affect dendritic cell differentiation from murine hematopoietic stem/progenitor cells (2011)
  • Author(s): Fujita J, Mizuki M, Otsuka M, Ezoe S, Tanaka H, Satoh Y, Fukushima K, Tokunaga M, Matsumura I, Kanakura Y
  • Journal Title: Immunol Lett Volume: 136 Pages: 61-73
  • Peer Reviewed
• [Journal Article] Constitutive active FGFR3 Lys650Glu mutation enhances the bortezomib-sensitivity in plasma cell malignancy (2011)
  • Author(s): Otsuka M, Mizuki M, Fujita J, Kang S, Kanakura Y
  • Journal Title: Anticancer Res Volume: 31 Pages: 113-122
  • Peer Reviewed
• [Journal Article] A cell-death-defying factor, anamorsin mediates cell growth through inactivation of PKC and p38MAPK (2011)
  • Author(s): Saito Y, Shibayama H, Tanaka H, Tanimura A, Kanakura Y
  • Journal Title: Biochem Biophys Res Commun Volume: 405 Pages: 303-307
  • Peer Reviewed
• [Journal Article] PICOT is a molecule which binds to anamorsin (2011)
  • Author(s): Saito Y, Shibayama H, Tanaka H, Tanimura A, Matsumura I, Kanakura Y
  • Journal Title: Biochem Biophys Res Commun Volume: 408 Pages: 329-333
  • Peer Reviewed
• [Journal Article] Bleeding tendency and impaired platelet function in a patient carrying a heterozygous mutation in the thromboxane A2 receptor (2011)
  • Author(s): Kamae T, Kiyomizu K, Nakazawa T, Tadokoro S, Kashiwagi H, Honda S, Kanakura Y, Tomiyama Y
  • Journal Title: J Thromb Haemost Volume: 9 Pages: 1040-1048
  • Peer Reviewed
• [Journal Article] BCR-ABL but not JAK2 V617F inhibits erythropoiesis through the Ras signal by inducing p21CIP1/WAF1 (2010)
  • Author(s): Tokunaga M, Ezoe S, Tanaka H, Satoh Y, Fukushima K, Matsui K, Shibata M, Tanimura A, Oritani K, Matsumura I, Kanakura Y
  • Journal Title: J Biol Chem Volume: 285 Pages: 31774-31782
  • Peer Reviewed
• [Journal Article] Stromal cell-free conditions favorable for human B lymphopoiesis in culture. (2010)
  • Author(s): Ichii M, Oritani K, Yokota T, Schultz DC, Holter JL, Kanakura Y, Kincade PW
  • Journal Title: J Immunol Methods Volume: 359 Pages: 47-55
  • Peer Reviewed
• [Journal Article] The density of CD10 corresponds to commitment and progression in the human B lymphoid lineage (2010)
  • Author(s): Ichii M, Oritani K, Yokota T, Zhang Q, Garrett KP, Kanakura Y, Kincade PW
  • Journal Title: PLoS One Volume: 5 Pages: e12954
  • Peer Reviewed
• [Journal Article] Diffuse large B-cell lymphoma in the spinal epidural space: A study of the Osaka Lymphoma Study Group (2010)
  • Author(s): Wada N, Kohara M, Ikeda J, Hori Y, Fujita S, Okada M, Ogawa H, Sugiyama H, Fukuhara S, Kanamaru A, Hino M, Kanakura Y, Morii E, Aozasa K
  • Journal Title: Pathol Res Pract Volume: 206 Pages: 439-444
  • Peer Reviewed
• [Presentation] An anti-apoptotic molecule, Anamorsin, is essential for erythropoiesis through the regulation of cellular labile iron pool. (2012)
  • Author(s): Tanimura A, Hamanaka Y, Fujita N, Doi Y, Ishibashi T, Sudo T, Matsui K, Ichii M, Saitoh N, Satoh Y, Ezoe S, Yokota T, Oritani K, Shibayama H, Kanakura Y
  • Organizer: The American Society of Hematology 54th Annual Meeting
  • Place of Presentation: Atlanta, USA
  • Year and Date: 2012-12-10
• [Presentation] A rare genetic polymorphism in C5 confers poor response to the anti-C5 monoclonal antibody eculizumab by nine Japanese patients with PNH (2012)
  • Author(s): Nishimura J, Yamamoto M, Hayashi S, Ohyashiki K, Ando K, Noji H, Kitamura K, Eto T, Ando T, Masuko M, Shibayama H, Hase M, Lan L, Tamburini P, Inazawa J, Kinoshita T, Kanakura Y
  • Organizer: The American Society of Hematology 54th Annual Meeting
  • Place of Presentation: Atlanta, USA
  • Year and Date: 2012-12-10
• [Presentation] An anti-apoptotic molecule, Anamorsin, functions in both Fe/S cluster assembly and iron homeostasis. (2012)
  • Author(s): Tanimura A, Hamanaka Y, Tanaka H, Matsumura I, Ishibashi T, Sudo T, Satoh Y, Yokota T, Ezoe S, Oritani K, Shibayama H, Kanakura Y
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2012-10-20
• [Presentation] Role of endothelial antigen ESAM in hematopoietic stem cells status (2012)
  • Author(s): Sudo T, Yokota T, Oritani K, Satoh Y, Sugiyama T, Ishida T, Shibayama H, Ezoe S, Ichii M, Tanimura A, Fujita N, Ishibashi T, Matsui K, Hamanaka Y, Nagasawa T, Kanakura Y
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2012-10-20
• [Presentation] Significance of novel HSC marker ESAM expression in cord blood (2012)
  • Author(s): Ishibashi T, Yokota T, Satoh Y, Sudo T, Ichii M, Shibayama H, Ezoe S, Tanimura A, Fujita N, Matsui K, Hamanaka Y, Oritani K, Kanakura Y
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2012-10-19
• [Presentation] Identification of osteoblast stimulating factor-5 as a novel regulator of early lymphocyte development (2012)
  • Author(s): Fujita N, Oritani K, Yokota T, Saito N, Sudo T, Yamawaki K, Kanakura Y
  • Organizer: The 17th Congress of the European Hematology Association
  • Place of Presentation: Amsterdam,Netherlands
  • Year and Date: 2012-06-15
• [Presentation] Involvement of STAP-2 in BCR-ABL-mediated signals for CML development (2012)
  • Author(s): Oritani K, Sekine Y, Muromoto R, Fujita N, Matsuda T, Kanakura Y
  • Organizer: 第3回日本血液学会(JSH)国際シンポジウム
  • Place of Presentation: 埼玉
  • Year and Date: 2012-05-26
• [Presentation] Satb1 promotes hematopoietic stem cell differentiation toward the lymphoid lineages (2011)
  • Author(s): Satoh Y, Yokota T, Kondo M, Lai A, Kincade P, Kouro T, Iida R, Kokame K, Miyata T, Sudo T, Tanaka H, Matsumura I, Oritani K, Kohwi-Shigematsu T, Kanakura Y
  • Organizer: The American Society of Hematology 53rd Annual meeting
  • Place of Presentation: San Diego, USA
  • Year and Date: 2011-12-10
• [Presentation] An anti-apoptotic molecule, Anamorsin, functions in both iron-sulfur protein assembly and cellular iron homeostasis (2011)
  • Author(s): Tanimura A, Kondo Y, Tanaka H, Matsumura I, Ishibashi T, Sudo T, Satoh Y, Yokota T, Ezoe S, Oritani K, Shibayama H, Kanakura Y
  • Organizer: The American Society of Hematology 53rd Annual meeting
  • Place of Presentation: San Diego, USA
  • Year and Date: 2011-12-10
• [Presentation] The endothelial antigen ESAM monitors reversible conversion of hematopoietic stem cells between dormancy and self-renewal (2011)
  • Author(s): Sudo T, Yokota T, Sugiyama T, Ishida T, Satoh Y, Oritani K, Nagasawa T, Kanakura Y
  • Organizer: The American Society of Hematology 53rd Annual meeting
  • Place of Presentation: San Diego, USA
  • Year and Date: 2011-12-10
• [Presentation] Satb1 directs hematopoietic stem cell differentiation toward the lymphoid lineages (2011)
  • Author(s): Yokota T, Satoh Y, Kondo M, Kincade PW, Kouro T, Iida R, Sudo T, Tanaka H, Matsumura I, Oritani K, Kohwi-Shigematsu T, Kanakura Y
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-27
• [Presentation] SATB1 induces early lymphocyte differentiation from primitive hematopoietic progenitors (2011)
  • Author(s): Satoh Y, Yokota T, Tanaka H, Kokame K, Miyata T, Matsumura I, Oritani K, Kanakura Y
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 愛知
  • Year and Date: 2011-10-14
• [Presentation] Predictability of the response to tyrosine kinase inhibitors via in vitro analysis of Bcr-Abl signal (2011)
  • Author(s): Shibata M, Ezoe S, Matsui K, Satoh Y, Tanimura A, Matsumura I, Oritani K, Kanakura Y
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 愛知
  • Year and Date: 2011-10-14
• [Presentation] Energy metabolism of glucose and ATP affects the growth and differentiation of hematopoietic stem/progenitor cells (2011)
  • Author(s): Matsui K, Ezoe S, Shibata M, Otsuka M, Oritani K, Kanakura Y
  • Organizer: The 16th Congress of the European Hematology Association
  • Place of Presentation: London, UK
  • Year and Date: 2011-06-09
• [Presentation] Constitutive active FGFR3 Lys650Glu mutation enhances the bortezomib-sensitivity in plasma cell malignancy (2011)
  • Author(s): Otsuka M, Mizuki M, Fujita J, Kang S, Kanakura Y
  • Organizer: The 16th Congress of the European Hematology Association
  • Place of Presentation: London, UK
  • Year and Date: 2011-06-09
• [Presentation] A cell-death-defying factor, anamorsin, contributes cell growth through binding with PICOT and inactivation of PKCs and p38MAPK (2010)
  • Author(s): Shibayama H, Saito Y, Tanimura A, Tanaka H, Matsumura I, Kanakura Y
  • Organizer: The American Society of Hematology 52nd Annual meeting
  • Place of Presentation: Orlando, USA
  • Year and Date: 2010-12-04
• [Presentation] A chromatin modifier SATB1 promotes lymphocyte production from primitive hematopoietic stem/ progenitor cells. (2010)
  • Author(s): Satoh Y, Yokota T, Tanaka H, Kokame K, Miyata T, Matsumura I, Oritani K, Kanakura Y
  • Organizer: The American Society of Hematology 52nd Annual meeting
  • Place of Presentation: Orlando, USA
  • Year and Date: 2010-12-04
• [Presentation] 骨髄不全の診断と治療 (2010)
  • Author(s): 金倉 譲
  • Organizer: 第42回日本内科学会近畿生涯教育講演会
  • Place of Presentation: 大阪
  • Year and Date: 2010-06-20
• [Presentation] Fatigue and impared quality of life in patients with paroxysmal nocturnal hemoglobinuria (PNH) is associated with hemolysis, but not with anemia. (2010)
  • 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 C, Valentine ME, Ozawa K, Omine M
  • Organizer: The 15th Congress of the European Hematology Association
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2010-06-10
• [Presentation] Essential role of an anti-apoptotic molecule Anamorsin for both intrinsic and extrinsic regulation of murine fetal liver hematopoiesis (2010)
  • Author(s): Tanimura A, Tanaka H, Saito Y, Shibayama H, Matsumura I, Kanakura Y
  • Organizer: The 15th Congress of the European Hematology Association
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2010-06-10
• [Book] Advances in Hematopoietic Stem Cell Research (2012)
  • Author(s): Yokota T, Oritani K, Butz S, Ewers S, Vestweber D, Kanakura Y
  • Total Pages: 77-88
  • Publisher: Intech Open Access Publisher
• [Remarks] 大阪大学大学院医学系研究科 血液・腫瘍内科学ホームページ アドレス:
  • URL: http://www.hematology.pro