Pathophysiology of myelodyspoastic syndrome - network between bone marrow and nervus system

• Project/Area Number: 23659482
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: University of Tsukuba
• Principal Investigator: CHIBA Shigeru 筑波大学, 医学医療系, 教授 (60212049)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: ネスチン / 骨髄異形成症候群 / 骨髄異形性症候群 / Nestin / 癌 / 細胞・組織

Research Abstract

In normal human bone marrow, spindle-shaped nestin-expressing cells, distinct from endothelial cells, were shown as the vascular vessel wall-constituting cells. In contrast, such a structure was disarranged in the bone marrow of myelodyspoastic syndrome patients. We further found abnormalities in fetal liver hematopoiesis in mice with knocked-down Notch signaling in cells expressing nestin, implying important roles of Notch signaling in nestin-expressing stromal cells in hematopoiesis.

Research Products

• [Journal Article] Identification of unbalanced genome copy number abnormalities in patients with multiple myeloma by single-nucleotide polymorphism genotyping microarray analysis (2012)
  • Author(s): Yuhei Kamada
  • Journal Title: IntJ Hematol Volume: 96 Pages: 492-500
  • DOI: 10.1007/s12185-012-1171-1
  • Peer Reviewed
• [Journal Article] Notch2 and immune function (2012)
  • Author(s): Mamiko Sakata-Yanagimoto
  • Journal Title: Curr Top Bicrobiol Immunol Volume: 360 Pages: 151-161
  • DOI: 10.1007/82_2012_235
  • Peer Reviewed
• [Journal Article] Differential regulation of osteoclastogenesis by Notch2/Delta-like 1 and Notch1/Jagged1 axes (2012)
  • Author(s): Sekine C, Koyanagi A, Koyama N, Hozumi K, Chiba S, Yagita H
  • Journal Title: Arthritis Res Ther Volume: Vol.14
  • DOI: 10.1186/ar3758
  • Peer Reviewed
• [Journal Article] Notch2 regulates the development of marginal zone B cells through Fos (2012)
  • Author(s): Iwahashi S, Maekawa Y, Nishida J, Ishifune C, Kitamura A, Arimochi H, Kataoka K, Chiba S, Shimada M, Yasutomo K
  • Journal Title: Biochem Biophys Res Commun Volume: 418 Pages: 701-707
  • Peer Reviewed
• [Journal Article] Neutralization of the γ-secretase activity by monoclonal antibody against extracellular domain of nicastrin (2012)
  • Author(s): Hayashi I, Takatori S, Urano Y, Miyake Y, Takagi J, Sakata-Yanagimoto M, Iwanari H, Osawa S, Morohashi Y, Li T, Wong PC, Chiba S, Kodama T, Hamakubo T, Tomita T, Iwatsubo T
  • Journal Title: Oncogene Volume: 31 Pages: 787-798
  • Peer Reviewed
• [Journal Article] Treatment outcome of adult Burkitt lymphoma in Japanese patients with modified LMB protocol: a single center retrospective analysis. (2011)
  • Author(s): Nishikii H, Nakamura N, Kondo Y, Okoshi Y, Suzukawa K, Hasegawa Y, Yokoyama Y, Sakata-Yanagimoto S, Enami T, Noguchi M, Chiba S
  • Journal Title: J Clin Exp Hematopathol Volume: 51 Pages: 109-114
  • Peer Reviewed
• [Journal Article] Frequent pathway mutations of splicing machinery in myelodysplasia (2011)
  • Author(s): Yoshida K, Sanada M, Shiraishi Y, Nowak D, Nagata Y, Yamamoto R, Sato Y, Sato-Otsubo A, Kon A, Nagasaki M, Chalkidis G, Suzuki Y, Shiosaka M, Kawahata R, Yamaguchi T, Otsu M, Obara N, Sakata-Yanagimoto M, Ishiyama K, Mori H, Nolte F, Hofmann WK, Miyawaki
  • Journal Title: Nature Volume: 478(7367) Pages: 64-69
  • Peer Reviewed
• [Journal Article] c-Maf plays a crucial role for the definitive erythropoiesis that accompanies erythroblastic island formation in the fetal liver (2011)
  • Author(s): Kusakabe M, Hasegawa K, Hamada M, Nakamura M, Ohsumi T, Suzuki H, Mai TT, Kudo T, Uchida K, Ninomiya H, Chiba S, Takahashi S
  • Journal Title: Blood Volume: 118 Pages: 1374-1385
  • Peer Reviewed
• [Journal Article] The LRF transcription factor regulates mature B cell development and the germinal center response in mice (2011)
  • Author(s): Sakurai N, Maeda M, Lee SU, Ishikawa Y, Li M, Williams JC, Wang L, Su L, Suzuki M, Saito TI, Chiba S, Casola S, Yagita H, Teruya-Feldstein J, Tsuzuki S, Bhatia R, Maeda T.
  • Journal Title: J Clin Invest Volume: 121 Pages: 2583-2598
  • Peer Reviewed
• [Journal Article] Treatment Outcome of Adult Burkitt Lymphoma in Japanese Patients with Modified LMB Protocol : A Single Center Retrospective Analysis (2011)
  • Author(s): Nishikii H, Nakamura N, Kondo Y, Okoshi Y, Suzukawa K, Hasegawa Y, Yokoyama Y, Sakata-Yanagimoto S, Enami T, Noguchi M, Chiba S
  • Journal Title: J Clin Exp Hematop. Volume: 51 Issue: 2 Pages: 109-114
  • DOI: 10.3960/jslrt.51.109
  • Peer Reviewed
• [Journal Article] Frequent pathway mutations of splicing machinery in myelodysplasia., Nature (2011)
  • Author(s): Kenichi Yoshida
  • Journal Title: Nature Volume: 478 Pages: 332-339
  • DOI: 10.1038/nature10496
  • Peer Reviewed
• [Journal Article] Notch-dependent and-independent regulation of mature B cell lineage fate and humoral immune response by the LRF transcription factor homodimer (2011)
  • Author(s): Nagisa Sakurai
  • Journal Title: J Clin Invest Volume: 121 Pages: 2581-2598
  • DOI: 10.1172/jci45682
  • Peer Reviewed
• [Journal Article] Procoagulant properties of microparticles released from red blood cells in paroxysmal nocturnal haemoglobinuria (2011)
  • Author(s): Yukinori Kozuma
  • Journal Title: British Journal of Haematology Volume: 152 Pages: 631-639
  • DOI: 10.1111/j.1365-2141.2010.08505.x
  • Peer Reviewed
• [Presentation] TET2 regulates erythropoiesis from human cord blood progenitors (2012)
  • Author(s): 榎並 輝和
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都
• [Presentation] Reduced Tet2 Function Contributes to Development of Peripheral T-Cell Lymphoma with Follicular Helper T-Cell-Like Features in Mice (2012)
  • Author(s): 武藤 秀治
  • Organizer: The American Society of Hematology 54th Annual Meeting and Exposition
  • Place of Presentation: Altanta, GA, USA
• [Presentation] Implication of the Distinct Differentiation Pathway of Megakaryocytes From Hematopoietic Stem Cells in the Mouse Bone Marrow (2012)
  • Author(s): 錦井 秀和
  • Organizer: The American Society of Hematology 54th Annual Meeting and Exposition
  • Place of Presentation: Altanta, GA, USA
• [Presentation] 国際的な臍帯血バンクネットワークを基盤とした臍帯血のやり取り (2012)
  • Author(s): 栗田尚樹, Francesco Frassoni, Nicoletta Sacchi, Claudia Cossu, Alberto Serio, Canieda Cilloni, 千葉滋, Maria Podesta
  • Organizer: 第34回日本造血幹細胞移植学会
  • Place of Presentation: 大阪
• [Presentation] First-Line Treatment and Outcome of Elderly Patients with Primary Central Nervous System Lymphoma (PCNSL) - A Systematic Review and Individual Patient Data Meta-Analysis (2012)
  • Author(s): Benjamin Kasenda
  • Organizer: The American Society of Hematology 54th Annual Meeting and Exposition
  • Place of Presentation: Georgia World Congress Center. Atlanta, USA
  • Year and Date: 2012-12-11
• [Presentation] Recurrent Mutations of Multiple Components of Cohesin Complex in Myeloid Neoplasms. (2012)
  • Author(s): Ayana Kon
  • Organizer: The American Society of Hematology 54th Annual Meeting and Exposition.
  • Place of Presentation: Georgia World Congress Center. Atlanta, USA
  • Year and Date: 2012-12-11
• [Presentation] Soluble Recombinant Thrombomodulin Is a Potentially Promising Agent without Causing Severe Hemorrhagic Events for Hematological Malignancy-Induced Disseminated Intravascular Coagulation (2012)
  • Author(s): Naoki Kurita
  • Organizer: The American Society of Hematology 54th Annual Meeting and Exposition
  • Place of Presentation: Georgia World Congress Center. Atlanta, USA
  • Year and Date: 2012-12-11
• [Presentation] Implication of the Distinct Differentiation Pathway of Megakaryocytes From Hematopoietic Stem Cells in the Mouse Bone Marrow (2012)
  • Author(s): Hidekazu Nishikii
  • Organizer: The American Society of Hematology 54th Annual Meeting and Exposition.
  • Place of Presentation: Georgia World Congress Center. Atlanta, USA
  • Year and Date: 2012-12-11
• [Presentation] Transcription Factor Hes1 Functions As a Tumor Suppressor in MLL-Associated Acute Leukemia (2012)
  • Author(s): Takayasu Kato
  • Organizer: The American Society of Hematology 54th Annual Meeting and Exposition.
  • Place of Presentation: Georgia World Congress Center. Atlanta, USA
  • Year and Date: 2012-12-11
• [Presentation] Reduced Tet2 Function Contributes to Development of Peripheral T-Cell Lymphoma with Follicular Helper T-Cell-Like Features in Mice (2012)
  • Author(s): Hideharu Muto
  • Organizer: The American Society of Hematology 54th Annual Meeting and Exposition.
  • Place of Presentation: Georgia World Congress Center. Atlanta, USA
  • Year and Date: 2012-12-11
• [Presentation] Detection of PNH-type cells using high-resolution flow cytometry: Interim analysis of OPTIMA study (2012)
  • Author(s): Kohei Hosokawa
  • Organizer: 第74回日本血液学会学術集会.
  • Place of Presentation: 京都京都国際会議場
  • Year and Date: 2012-10-21
• [Presentation] Spectrum of gene mutations in myelodysplastic syndromes revealed by whole-exome sequencing (2012)
  • Author(s): Kenichi Yoshida
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都国際会議場. 京都
  • Year and Date: 2012-10-21
• [Book] Medical Practice「実地医家のための臨床検査のすすめかた・評価のしかた (2012)
  • Author(s): 小原直
  • Publisher: 文光堂
• [Book] 最新医学別冊 (2011)
  • Author(s): 千葉滋
  • Publisher: 最新医学社
• [Book] Embryonic Stem Cells - Recent Advances in Pluripotent Stem Cell-Base Regenerative Medicine (2011)
  • Author(s): Craig S. Atwood
  • Total Pages: 410
  • Publisher: INTECH (Viena)
• [Book] 造血幹細胞移植の基礎と臨床(改訂版) (2010)
  • Author(s): 錦井秀和
  • Publisher: 医薬ジャーナル社
• [Remarks]
  • URL: http://www.ketsunai.com
• [Remarks]
  • URL: http://www.md.tsukuba.ac.jp/hematology/