Where and how are mature platelets produced?

• Project/Area Number: 25461458
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Iwate Medical University
• Principal Investigator: Ishida Yoji 岩手医科大学, 医学部, 教授 (70151389)
• Co-Investigator(Kenkyū-buntansha): KOWATA Syugo 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) ; ITO Shigeki 岩手医科大学, 医学部腫瘍内科学科, 教授 (60316362)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 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

Outline of Final Research Achievements

How and where mature platelets are produced were investigated. Two evidences were obtained. The first, megakaryocytes in the bone marrow extended the proplatelets into the sinusoid and the proplatelet snapped, resulting in the immature platelets were released into the sinusoid in a steady state. The second, in the emergency state, in which a lot of platelets were demanded in thrombocytopenia, another immature platelets called "thick protrusion" were released into the sinusoid. These two types of immature platelets were converted into the mature platelets in the circulation.

Research Products

• [Journal Article] Pharmacokinetics and pharmacodynamics of dasatinib in the chronic phase of newly diagnosed chronic myeloid leukemia. (2016)
  • Author(s): 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)
  • Journal Title: Eur J Clin Pharmacol. Volume: 72 Issue: 2 Pages: 185-193
  • DOI: 10.1007/s00228-015-1968-y
  • Peer Reviewed
• [Journal Article] Comparison of micafangin and voriconazole as emperic therapies in febrile neutropenia in patients with hematological disorders: a randomized controlled trial. (2016)
  • Author(s): Oyake T, Kowata S, Murai K, Ito S, Akagi T, Kubo K, Sawada K, Ishida Y.
  • Journal Title: Eur J Haematol Volume: 96 Issue: 6 Pages: 602-609
  • DOI: 10.1111/ejh.12641
  • Peer Reviewed
• [Journal Article] 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)
  • Author(s): 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
  • Journal Title: Eur J Haematol Volume: Feb 19 Issue: 6 Pages: 12536-12536
  • DOI: 10.1111/ejh.12536
  • Peer Reviewed / Open Access
• [Journal Article] YM155 suppresses cell proliferation and induces cell death in human adult T-cell leukemia/lymphoma cells (2015)
  • Author(s): Sasaki R, Ito S, Asahi M, Ishida Y
  • Journal Title: Leuk Res Volume: 39 Issue: 12 Pages: 1473-1479
  • DOI: 10.1016/j.leukres.2015.10.012
  • Peer Reviewed
• [Journal Article] 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)
  • Author(s): 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
  • Journal Title: Lancet Haematology Volume: 2 Issue: 12 Pages: e528-e535
  • DOI: 10.1016/s2352-3026(15)00196-9
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 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)
  • Author(s): 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.
  • Journal Title: Int J Hematol Volume: 99 Issue: 2 Pages: 141-153
  • DOI: 10.1007/s12185-013-1470-1
  • Peer Reviewed
• [Journal Article] Platelet demand modulates the type of intravascular protrusion of megakaryocytes in bone marrow (2014)
  • Author(s): Kowata S, Isogai S, Murai K, Ito S, Tohyama K, Ema M, Hitomi J and Ishida Y
  • Journal Title: Thrombosis and Haemostasis Volume: 112 Issue: 10 Pages: 743-756
  • DOI: 10.1160/th14-02-0123
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Bortezomib induces thrombocytopenia by the inhibition of proplatelet formation of megakaryocytes (2014)
  • Author(s): Kazunori Murai, Shugo Kowata, Tadashi Shimoyama, Akiko Yashima-Abo, Yukiteru Fujishima, Shigeki Ito, and Yoji Ishida
  • Journal Title: Eur J Haematol Volume: ? Issue: 4 Pages: 290-296
  • DOI: 10.1111/ejh.12342
  • Peer Reviewed
• [Journal Article] Classical Hodgkin lymphoma occurring in association with progressive transformation of germinal center (2014)
  • Author(s): Yashima-Abo A, Satoh T, Shimosegawa K, Ishida Y, Masuda, T
  • Journal Title: J Clin Exp Hematop Volume: 54 Pages: 205-209
  • NAID: 130004705267
  • Peer Reviewed
• [Journal Article] Platelet demand modulates the type of intravascular protrusion of megakaryocytes in bone marrow (2014)
  • Author(s): Shugo Kowata, Sumio Isogai, Kazunori Murai, Shigeki Ito, Koujiro Tohyama, Masatsugu Ema, Jiro Hitomi, and Yoji Ishida
  • Journal Title: Thrombosis and Haemostasis Volume: ?
  • Peer Reviewed
• [Journal Article] Resveratrol suppresses cell proliferation via inhibition of STAT3 phosphorylation and Mcl-1 and cIAP-2 expression in HTLV-1-infected T cells (2013)
  • Author(s): Suzuki, Y. Ito, S. Sasaki, R. Asahi, M. Ishida, Y.
  • Journal Title: Leuk Res Volume: 37 Issue: 12 Pages: 1674-79
  • DOI: 10.1016/j.leukres.2013.09.010
  • Peer Reviewed
• [Journal Article] World’s first telepathology experiments employing ultra-high-speed internet satellite, nickenemaed “KIZUNA”. (2013)
  • Author(s): 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
  • Journal Title: J Pathol Inform Volume: 4 Issue: 1 Pages: 24-24
  • DOI: 10.4103/2153-3539.119002
  • Peer Reviewed / Open Access
• [Journal Article] Successful use of cyclophosphamide as an add-on therapy for multiple myeloma patients with acquired resistance to bortezomib or lenalidomide. (2013)
  • Author(s): Ito S, Oyake T, Murai K, IshidaY
  • Journal Title: Case Rep Hematol Volume: 65 Pages: 1902-1902
  • DOI: 10.1155/2013/651902
  • Peer Reviewed
• [Presentation] 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)
  • Author(s): 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,
  • Organizer: 57th Annual Meeting of America Society of Hematology
  • Place of Presentation: Orland, FL, USA
  • Year and Date: 2015-12-07
  • Int'l Joint Research
• [Presentation] Recombinant Thrombomodulin for the Treatment of Transplantation-Associated Coagulopathy after Allogeneic Hematopoietic Stem Cell Transplantation: A Multi-Center Study in Japan (2015)
  • Author(s): 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,
  • Organizer: 57th Annual Meeting of America Society of Hematology
  • Place of Presentation: Orland, FL, USA
  • Year and Date: 2015-12-07
  • Int'l Joint Research
• [Presentation] Platelet Progenitors after Leaving Bone Marrow (2015)
  • Author(s): Shugo Kowata, Ryo Togawa, Yoshiaki Okano, Sumio Isogai, Jiro Hitomi, Kazunori Murai, Shigeki Ito, Yoji Ishida,
  • Organizer: 57th Annual Meeting of America Society of Hematology
  • Place of Presentation: Orland, FL, USA
  • Year and Date: 2015-12-06
  • Int'l Joint Research
• [Presentation] PLATELET PROGENITORS AFTER LEAVING BONE MARROW (2015)
  • Author(s): Kowata S, Murai K, Oyake T, Ito S, Ishida Y
  • Organizer: the 20th Congress of the European Hematology Association
  • Place of Presentation: Vienna
  • Year and Date: 2015-06-11 – 2015-06-14
• [Presentation] COMPARISON OF MICAFUNGIN AND LIPOSOMAL AMPHOTERICIN B FOR EMPIRICAL ANTIFUNGAL THERAPY IN FEBRILE NEUTROPENIC PATIENTS WITH HEMATOLOGICAL MALIGNANCIES: A RANDOMIZED CONTROLLED TRIAL (2015)
  • Author(s): Fujisawa Y, Tatsuo Oyake T, Sugawara N, Sasaki R, Tsukushi Y, Hanamura I, Fujishima Y, Aoki Y, Kowata1 S, Ito S, Ishida Y
  • Organizer: the 20th Congress of the European Hematology Association
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2015-06-11 – 2015-06-14
• [Presentation] DORIPENEM VERSUS MEROPENEM AS THE FIRST-LINE MONO-THERAPY IN HIGH-RISK FEBRILE NEUTROPENIC PATIENTS WITH ACUTE LEUKEMIA: A RANDOMIZED, CONTROLLED TRIAL (2015)
  • Author(s): 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
  • Organizer: the 20th Congress of the European Hematology Association
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2015-06-11 – 2015-06-14
• [Presentation] Platelet Progenitors after Leaving Bone Marrow (2015)
  • Author(s): Kowata S, Murai K, Oyake T, Ito S, Ishida Y
  • Organizer: 20th Congress of the European Hematology Association
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2015-06-11
  • Int'l Joint Research
• [Presentation] Comparison of micafungin and liposome amphotericin B for empirical anti fungal therapy in febrile neutropenic patients with hematological malignancies: A randomized controlled study (2015)
  • Author(s): Fujisawa Y, Oyake T, Sugawara N, Sasaki R, Tsukushi Y, Hanamura I, Fujishima Y, Aoki Y, Kowata S, Ito S, Ishida Y
  • Organizer: 20th Congress of the European Hematology Association
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2015-06-11
  • Int'l Joint Research
• [Presentation] Doripenemu versus meropenem as the first-line mono-therapy in high risk febrile neutropenic patients with acute leukemia : A randomized, controlled study (2015)
  • Author(s): 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
  • Organizer: 20th Congress of the European Hematology Association
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2015-06-11
  • Int'l Joint Research
• [Presentation] Dasatinib Is Effective in theTreatment of Mice Models with Immune Thrombocytopenia (2014)
  • Author(s): Shimoyama T, Okano Y, Fujishima Y, Oyake T,Kowata S, Murai K, Ito S, and Ishida Y
  • Organizer: 56th American Society of Hematology Meeting and Exoosition
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2014-12-05 – 2014-12-09
• [Presentation] ndex to Predict MMR at 12 Months in Chronic Phase Chronic Myeloid Leukemia Patients Based on the Area Under the Lymphocyte Curve (2014)
  • Author(s): Murai K, Ito S, Kowata S, Oyake T and Ishida Y,
  • Organizer: 56th American Society of Hematology Meeting and Exoosition
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2014-12-05 – 2014-12-09
• [Presentation] Clinical Efficacy and Safety Of Dasatinib For Newly Diagnosed Chronic Myeloid Leukemia In Chronic Phase In Japa (2013)
  • Author(s): 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
  • Organizer: 55th ASH annual Meeting and Exposition
  • Place of Presentation: New Orleans
• [Presentation] 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)
  • Author(s): 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
  • Organizer: 55th ASH annual Meeting and Exposition
  • Place of Presentation: New Orleans
• [Presentation] Pharmacokinetic (PK) & Pharmacodynamic (PD) analysis of Dasatinib in Chronic Phase of Newly Diagnosed Chronic Myeloid Leukemia (CML-CP) (2013)
  • Author(s): 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)
  • Organizer: 55th ASH annual Meeting and Exposition
  • Place of Presentation: New Orleans
• [Presentation] 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)
  • Author(s): 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
  • Organizer: 55th ASH annual Meeting and Exposition
  • Place of Presentation: New Orleans
• [Presentation] Dasatinib Induced Thrombocytopenia Might Be Due To The Inhibition Of Proplatelet Formation Of Megakaryocytes Via The Pathways Including Rho/Rock and Rac (2013)
  • Author(s): Kazunori Murai, Shugo Kowata, Yukiteru Fujishima, Yasuhiko Tsukushi, Takahiro Mine, Tatsuo Oyake, Shigeki Ito, and Yoji Ishida
  • Organizer: 55th ASH annual Meeting and Exposition
  • Place of Presentation: New Orleans
• [Presentation] YM155, a Survivin Suppressant, Induces Cell Death Via Suppression Of c-Myc Expression In Multiple Myeloma Cells (2013)
  • Author(s): Shigeki Ito, Maki Asahi, Ryousei Sasaki, Tatsuo Oyake, Hideto Tamura, and Yoji Ishida
  • Organizer: 55th ASH annual Meeting and Exposition
  • Place of Presentation: New Orleans