血小板はどこでどのように産生されるか

• 研究課題/領域番号: 25461458
• 研究種目: 基盤研究(C)
• 配分区分: 基金
• 応募区分: 一般
• 研究分野: 血液内科学
• 研究機関: 岩手医科大学
• 研究代表者: 石田 陽治 岩手医科大学, 医学部, 教授 (70151389)
• 研究分担者: 古和田 周吾 岩手医科大学, 医学部内科学講座血液腫瘍内科分野, 教授 (30418884) ; 伊藤 薫樹 岩手医科大学, 医学部腫瘍内科学科, 教授 (60316362)
• 研究期間 (年度): 2013-04-01 – 2016-03-31
• 研究課題ステータス: 完了 (2015年度)
• 配分額: 4,940千円 (直接経費: 3,800千円、間接経費: 1,140千円); 2015年度: 1,170千円 (直接経費: 900千円、間接経費: 270千円); 2014年度: 1,690千円 (直接経費: 1,300千円、間接経費: 390千円); 2013年度: 2,080千円 (直接経費: 1,600千円、間接経費: 480千円)
• キーワード: megakaryocyte / thrombocytopoiesis / proplatelet / thick protrusion / immature platelet / 血小板産生 / preplatelet / 血小板造血 / 巨核球 / 血小板前駆体 / 成熟血小板

研究成果の概要

骨髄巨核球からいかにして血小板が産生されるかを検討した。明らかになったのは点は以下の点である。通常は、骨髄巨核球は胞体突起と呼ばれる突起を静脈洞に進展させ、それが切断されて血小板前駆体を放出する。血小板減少が起こり、短期間に血小板が必要な場合は、thick protrusionと呼ばれる、巨核球細胞質の一部を静脈洞に放出する。これらの２つの血小板前駆体は、循環床のどこかで成熟血小板に変化するものと考えられた。

研究成果

• [雑誌論文] Pharmacokinetics and pharmacodynamics of dasatinib in the chronic phase of newly diagnosed chronic myeloid leukemia. (2016)
  • 著者名/発表者名: Ishida Y, Murai K, Yamaguchi K, Miyagishima T, Shindo M, Ogawa K, Nagashima T, Sato S, Watanabe R, Yamamoto S, Hirose T, Saitou S, Yonezumi M, Kondo T, Kato Y, Mochizuki N, Ohno K, Kishino S, Kubo K, Oyake T, Ito S; Inter-Michinoku Dasatinib Study Group (IMIDAS)
  • 雑誌名: Eur J Clin Pharmacol. 巻: 72 号: 2 ページ: 185-193
  • DOI: 10.1007/s00228-015-1968-y
  • 査読あり
• [雑誌論文] Comparison of micafangin and voriconazole as emperic therapies in febrile neutropenia in patients with hematological disorders: a randomized controlled trial. (2016)
  • 著者名/発表者名: Oyake T, Kowata S, Murai K, Ito S, Akagi T, Kubo K, Sawada K, Ishida Y.
  • 雑誌名: Eur J Haematol 巻: 96 号: 6 ページ: 602-609
  • DOI: 10.1111/ejh.12641
  • 査読あり
• [雑誌論文] A prospective analysis of clinical efficacy and safety in chronic myeloid leukemia-chronic phase patients with imatinib resistance or intolerance as evaluated using European LeukemiaNet 2013 criteria (2015)
  • 著者名/発表者名: 2.Murai K, Akagi T, Shimosegawa K, Sugawara T, Ishizawa K, Ito S, Murai K, Motegi M, Yokoyama H, Noji H, Tajima K, Kimura J, Chou T, Ogawa K, Harigae H, Kubo K, Oba K, Sakamoto J, Ishida Y
  • 雑誌名: Eur J Haematol 巻: Feb 19 号: 6 ページ: 12536-12536
  • DOI: 10.1111/ejh.12536
  • 査読あり / オープンアクセス
• [雑誌論文] YM155 suppresses cell proliferation and induces cell death in human adult T-cell leukemia/lymphoma cells (2015)
  • 著者名/発表者名: Sasaki R, Ito S, Asahi M, Ishida Y
  • 雑誌名: Leuk Res 巻: 39 号: 12 ページ: 1473-1479
  • DOI: 10.1016/j.leukres.2015.10.012
  • 査読あり
• [雑誌論文] Discontinuation of dasatinib in patients with chronic myeloid leukaemia who have maintained complete molecular response for at least 1 year: the prospective, multicentre Dasatinib-Discontinuation (DADI) Trial (2015)
  • 著者名/発表者名: J Imagawa, H Tanaka, M Okada, H Nakamae, M Hino, K Murai, Y Ishida, T Kumagai, S Sato, K Ohashi, H Sakamaki, H Wakita, N Uoshima, Y Nakagawa, Y Minami, M Ogasawara, T Takeoka, H Akasaka, T Utsumi, N Uike, T Sato, H Sakai, K Usuki, S Morita, J Sakamoto, and S Kimura, on behalf of the DADI Trial Group, JAPAN
  • 雑誌名: Lancet Haematology 巻: 2 号: 12 ページ: e528-e535
  • DOI: 10.1016/s2352-3026(15)00196-9
  • 査読あり / 謝辞記載あり
• [雑誌論文] Efficacy and safety of dasatinib versus imatinib in Japanese patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP): Subset analysis of the DASISION trial with 2-year follow-up. (2014)
  • 著者名/発表者名: Fujisawa S, Nakamae H, Ogura M, Ishizawa K, Taniwaki M, Utsunomiya A, Matsue K, Takamatsu Y, Usuki K, Tanimoto M, Ishida Y, Akiyama H, Onishi S.
  • 雑誌名: Int J Hematol 巻: 99 号: 2 ページ: 141-153
  • DOI: 10.1007/s12185-013-1470-1
  • 査読あり
• [雑誌論文] Platelet demand modulates the type of intravascular protrusion of megakaryocytes in bone marrow (2014)
  • 著者名/発表者名: Kowata S, Isogai S, Murai K, Ito S, Tohyama K, Ema M, Hitomi J and Ishida Y
  • 雑誌名: Thrombosis and Haemostasis 巻: 112 号: 10 ページ: 743-756
  • DOI: 10.1160/th14-02-0123
  • 査読あり / 謝辞記載あり
• [雑誌論文] Bortezomib induces thrombocytopenia by the inhibition of proplatelet formation of megakaryocytes (2014)
  • 著者名/発表者名: Kazunori Murai, Shugo Kowata, Tadashi Shimoyama, Akiko Yashima-Abo, Yukiteru Fujishima, Shigeki Ito, and Yoji Ishida
  • 雑誌名: Eur J Haematol 巻: ? 号: 4 ページ: 290-296
  • DOI: 10.1111/ejh.12342
  • 査読あり
• [雑誌論文] Classical Hodgkin lymphoma occurring in association with progressive transformation of germinal center (2014)
  • 著者名/発表者名: Yashima-Abo A, Satoh T, Shimosegawa K, Ishida Y, Masuda, T
  • 雑誌名: J Clin Exp Hematop 巻: 54 ページ: 205-209
  • NAID: 130004705267
  • 査読あり
• [雑誌論文] Platelet demand modulates the type of intravascular protrusion of megakaryocytes in bone marrow (2014)
  • 著者名/発表者名: Shugo Kowata, Sumio Isogai, Kazunori Murai, Shigeki Ito, Koujiro Tohyama, Masatsugu Ema, Jiro Hitomi, and Yoji Ishida
  • 雑誌名: Thrombosis and Haemostasis 巻: ?
  • 査読あり
• [雑誌論文] Resveratrol suppresses cell proliferation via inhibition of STAT3 phosphorylation and Mcl-1 and cIAP-2 expression in HTLV-1-infected T cells (2013)
  • 著者名/発表者名: Suzuki, Y. Ito, S. Sasaki, R. Asahi, M. Ishida, Y.
  • 雑誌名: Leuk Res 巻: 37 号: 12 ページ: 1674-79
  • DOI: 10.1016/j.leukres.2013.09.010
  • 査読あり
• [雑誌論文] World’s first telepathology experiments employing ultra-high-speed internet satellite, nickenemaed “KIZUNA”. (2013)
  • 著者名/発表者名: Sawai T, Uzuki M, Miura Y, Kamataki A, Matsumura T, Saito K, Kurose A, Osamura YR, Yoshimi N, Kanno H, Moriya T, Ishida Y, Satoh Y, Nakao M, Ogawa E, Matsuo S, Kasai H, Kumagai K, Motoda T, Hopson N
  • 雑誌名: J Pathol Inform 巻: 4 号: 1 ページ: 24-24
  • DOI: 10.4103/2153-3539.119002
  • 査読あり / オープンアクセス
• [雑誌論文] Successful use of cyclophosphamide as an add-on therapy for multiple myeloma patients with acquired resistance to bortezomib or lenalidomide. (2013)
  • 著者名/発表者名: Ito S, Oyake T, Murai K, IshidaY
  • 雑誌名: Case Rep Hematol 巻: 65 ページ: 1902-1902
  • DOI: 10.1155/2013/651902
  • 査読あり
• [学会発表] Velocity of Early BCR-ABL Transcript Elimination As an Optimized Predictor of Deep Molecular Response in Chronic Myeloid Leukemia Patients in Chronic Phase on Treatment with Dasatinib (2015)
  • 著者名/発表者名: Kazunori Murai, Kohei Yamaguchi, Shigeki Ito, Tomoaki Akagi, Kazuei Ogawa, Inomata Mitsue, Kuniaki Meguro, Reiko Watanabe, Takuto Miyagishima, Kentaro Wakasa, Motohiro Shindo, Yasuhiko Tsukushi, Kohmei Kubo, Koji Oba, Junichi Sakamoto and Yoji Ishida,
  • 学会等名: 57th Annual Meeting of America Society of Hematology
  • 発表場所: Orland, FL, USA
  • 年月日: 2015-12-07
  • 国際学会
• [学会発表] Recombinant Thrombomodulin for the Treatment of Transplantation-Associated Coagulopathy after Allogeneic Hematopoietic Stem Cell Transplantation: A Multi-Center Study in Japan (2015)
  • 著者名/発表者名: Kazuyoshi Ishii, Shosaku Nomura, Shinya Fujita, Atushi Satake, Tomoki Ito, Yuta Katayama, Taiichi Kyo, Shuichi Ota, Masanori Seki, Shigeru Chiba, Yoshinobu Maeda, Mitsune Tanimoto, Takayuki Ikezoe, Hideo Yagi, Kunio Hayashi, Yoji Ishida, Naohito Fujishima, Kenichi Sawada, Masaya Okada, and Hiroyasu Ogawa,
  • 学会等名: 57th Annual Meeting of America Society of Hematology
  • 発表場所: Orland, FL, USA
  • 年月日: 2015-12-07
  • 国際学会
• [学会発表] Platelet Progenitors after Leaving Bone Marrow (2015)
  • 著者名/発表者名: Shugo Kowata, Ryo Togawa, Yoshiaki Okano, Sumio Isogai, Jiro Hitomi, Kazunori Murai, Shigeki Ito, Yoji Ishida,
  • 学会等名: 57th Annual Meeting of America Society of Hematology
  • 発表場所: Orland, FL, USA
  • 年月日: 2015-12-06
  • 国際学会
• [学会発表] PLATELET PROGENITORS AFTER LEAVING BONE MARROW (2015)
  • 著者名/発表者名: Kowata S, Murai K, Oyake T, Ito S, Ishida Y
  • 学会等名: the 20th Congress of the European Hematology Association
  • 発表場所: Vienna
  • 年月日: 2015-06-11 – 2015-06-14
• [学会発表] COMPARISON OF MICAFUNGIN AND LIPOSOMAL AMPHOTERICIN B FOR EMPIRICAL ANTIFUNGAL THERAPY IN FEBRILE NEUTROPENIC PATIENTS WITH HEMATOLOGICAL MALIGNANCIES: A RANDOMIZED CONTROLLED TRIAL (2015)
  • 著者名/発表者名: Fujisawa Y, Tatsuo Oyake T, Sugawara N, Sasaki R, Tsukushi Y, Hanamura I, Fujishima Y, Aoki Y, Kowata1 S, Ito S, Ishida Y
  • 学会等名: the 20th Congress of the European Hematology Association
  • 発表場所: Vienna, Austria
  • 年月日: 2015-06-11 – 2015-06-14
• [学会発表] DORIPENEM VERSUS MEROPENEM AS THE FIRST-LINE MONO-THERAPY IN HIGH-RISK FEBRILE NEUTROPENIC PATIENTS WITH ACUTE LEUKEMIA: A RANDOMIZED, CONTROLLED TRIAL (2015)
  • 著者名/発表者名: Sugawara N, Oyake T, Fujisawa Y, Sasaki R, Mine T, Tsukushi Y, Hanamura I, Asahi M, Suzuki Y, Okano Y, Fujishima Y, Aoki Y, Kowata S, Ito S, Ishida Y
  • 学会等名: the 20th Congress of the European Hematology Association
  • 発表場所: Vienna, Austria
  • 年月日: 2015-06-11 – 2015-06-14
• [学会発表] Platelet Progenitors after Leaving Bone Marrow (2015)
  • 著者名/発表者名: Kowata S, Murai K, Oyake T, Ito S, Ishida Y
  • 学会等名: 20th Congress of the European Hematology Association
  • 発表場所: Vienna, Austria
  • 年月日: 2015-06-11
  • 国際学会
• [学会発表] Comparison of micafungin and liposome amphotericin B for empirical anti fungal therapy in febrile neutropenic patients with hematological malignancies: A randomized controlled study (2015)
  • 著者名/発表者名: Fujisawa Y, Oyake T, Sugawara N, Sasaki R, Tsukushi Y, Hanamura I, Fujishima Y, Aoki Y, Kowata S, Ito S, Ishida Y
  • 学会等名: 20th Congress of the European Hematology Association
  • 発表場所: Vienna, Austria
  • 年月日: 2015-06-11
  • 国際学会
• [学会発表] Doripenemu versus meropenem as the first-line mono-therapy in high risk febrile neutropenic patients with acute leukemia : A randomized, controlled study (2015)
  • 著者名/発表者名: Sugawara N, Oyake T, Fujisawa Y, Sasaki R, Mine T, Tsukushi Y, Hanamura I, Asahi M, Suzuki Y, Okano Y, Fijishima Y, Aoki Y, Kowata S, Ito S, Ishida Y
  • 学会等名: 20th Congress of the European Hematology Association
  • 発表場所: Vienna, Austria
  • 年月日: 2015-06-11
  • 国際学会
• [学会発表] Dasatinib Is Effective in theTreatment of Mice Models with Immune Thrombocytopenia (2014)
  • 著者名/発表者名: Shimoyama T, Okano Y, Fujishima Y, Oyake T,Kowata S, Murai K, Ito S, and Ishida Y
  • 学会等名: 56th American Society of Hematology Meeting and Exoosition
  • 発表場所: San Francisco, USA
  • 年月日: 2014-12-05 – 2014-12-09
• [学会発表] ndex to Predict MMR at 12 Months in Chronic Phase Chronic Myeloid Leukemia Patients Based on the Area Under the Lymphocyte Curve (2014)
  • 著者名/発表者名: Murai K, Ito S, Kowata S, Oyake T and Ishida Y,
  • 学会等名: 56th American Society of Hematology Meeting and Exoosition
  • 発表場所: San Francisco, USA
  • 年月日: 2014-12-05 – 2014-12-09
• [学会発表] Clinical Efficacy and Safety Of Dasatinib For Newly Diagnosed Chronic Myeloid Leukemia In Chronic Phase In Japa (2013)
  • 著者名/発表者名: Kohei Yamaguchi, Kazunori Murai, Shigeki Ito, Tomoaki Akagi, , Kazuei Ogawa, Kuniaki Meguro, Mitsue Inomata, Reiko Watanabe, Takuto Miyagishima, Kentaro Wakasa, Motohiro Shindo, Yasuhiko Tsukushi, Kohmei Kubo, and Yoji Ishida
  • 学会等名: 55th ASH annual Meeting and Exposition
  • 発表場所: New Orleans
• [学会発表] The prospective analysis of clinical efficacy and adverse events in CML-CP patients with imatinib resistance or intolerance, evaluated by European LeukemicNet (ELN) 2013 criteria (2013)
  • 著者名/発表者名: Kazunori Murai, Tomoaki Akagi, Kenji Shimosegawa, Kenichi Ishizawa, Tomohiro Sugawara, Hisayuki Yokoyama, Hideyoshi Noji, Kazuei Ogawa, Katsushi Tajima, Koji Ooba, Junichi Sakamoto, Koumei Kubo, Hisashi Sakamaki, Hideo Harigae, and Yoji Ishida
  • 学会等名: 55th ASH annual Meeting and Exposition
  • 発表場所: New Orleans
• [学会発表] Pharmacokinetic (PK) & Pharmacodynamic (PD) analysis of Dasatinib in Chronic Phase of Newly Diagnosed Chronic Myeloid Leukemia (CML-CP) (2013)
  • 著者名/発表者名: Ishida Y, Murai K, Yamaguchi K, Miyagishima T, Shindo M, Ogawa K, Nagashima T, Sato S, Watanabe R, Yamamoto S, Hirose T, Saitou S, Yonezumi M, Kondo K, Kato Y, Mochizuki N, Ohno K, Kishino S, Ito S, Kubo K and Inter-Michinoku Dasatinib Study Group(IMIDAS)
  • 学会等名: 55th ASH annual Meeting and Exposition
  • 発表場所: New Orleans
• [学会発表] Discontinuation of Dasatinib in Patients with CML Who Have Maintained Complete Molecular Response for at least One Year: Results From a Prospective Discontinuation (DADI) Trial (2013)
  • 著者名/発表者名: Tanaka H, Imagawa J, Okada M, Nakamae H, Hino M, Murai K,Ishida Y, Kumagai T, Sato S, Ohashi K, Sakamaki H, Wakita H, Uoshima N, Nakagawa Y, Minami Y, Ogasawara M, Takeoka T, Akasaka H, Morita S, Sakamoto J, and Kimura S, on behalf of the DADI Trial Group, JAPAN
  • 学会等名: 55th ASH annual Meeting and Exposition
  • 発表場所: New Orleans
• [学会発表] Dasatinib Induced Thrombocytopenia Might Be Due To The Inhibition Of Proplatelet Formation Of Megakaryocytes Via The Pathways Including Rho/Rock and Rac (2013)
  • 著者名/発表者名: Kazunori Murai, Shugo Kowata, Yukiteru Fujishima, Yasuhiko Tsukushi, Takahiro Mine, Tatsuo Oyake, Shigeki Ito, and Yoji Ishida
  • 学会等名: 55th ASH annual Meeting and Exposition
  • 発表場所: New Orleans
• [学会発表] YM155, a Survivin Suppressant, Induces Cell Death Via Suppression Of c-Myc Expression In Multiple Myeloma Cells (2013)
  • 著者名/発表者名: Shigeki Ito, Maki Asahi, Ryousei Sasaki, Tatsuo Oyake, Hideto Tamura, and Yoji Ishida
  • 学会等名: 55th ASH annual Meeting and Exposition
  • 発表場所: New Orleans