Clarification of molecular pathogenesis of hematological diseases by analyzing functional role of myosin superfamily

• Project/Area Number: 24590703
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Kitasato University
• Principal Investigator: MIYAZAKI Koji 北里大学, 医学部, 講師 (90261966)
• Co-Investigator(Kenkyū-buntansha): HIGASHIHARA Masaaki 北里大学, 医学部, 教授 (80165084)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 血小板 / 細胞骨格 / 非筋ミオシン / 細胞内膜輸送 / proplatelet / 細胞骨格蛋白質

Outline of Final Research Achievements

We have shown the findings as follows. 1) myosinVI transferred into the nucleus from cytosol in non-secretion type of myeloma cells. This might be a possible mechanism how non-secretion type myeloma has a poor prognosis. 2) myosin II has an important role on CD3 expression on the plasma membrane and stabilization of immune synapse. 3) Knock-down of myosin IIB is enough to restore megakaryocyte differentiation in AML cells with RUNX1 mutation. 4) The tail mutations hampered the ATP-induced formation of foleded conformation thus stabilizing the myosin aggregates.

Research Products

• [Journal Article] Acute leukemia during pregnancy: an investigative survey of the past 11 years. (2015)
  • Author(s): Nakajima Y1, Hattori Y, Ito S, Ohshima R, Kuwabara H, Machida S, Shirasugi Y, Miyazaki K, Sakai R, Tomita N, Ando K, Higashihara M, Ishigatsubo Y, Fujisawa S.
  • Journal Title: Int J Lab Hematol. Volume: 37(2) Issue: 2 Pages: 174-180
  • DOI: 10.1111/ijlh.12256
  • Peer Reviewed / Open Access
• [Journal Article] IgA Paraneoplastic Pemphigus in Angioimmunoblastic T-cell Lymphoma with Antibodies to Desmocollin 1, Type VII Collagen and Laminin 332. (2014)
  • Author(s): Yashiro M, Nakano T, Taniguchi T, Katsuoka K, Tadera N, Miyazaki K, Teye K, Koga H, Hashimoto T.
  • Journal Title: Acta Derm Venereol. Volume: 94(2) Issue: 2 Pages: 235-236
  • DOI: 10.2340/00015555-1660
  • Peer Reviewed
• [Journal Article] ACTN1 Mutations Cause Congenital Macrothrombocytopenia (2013)
  • Author(s): 國島伸治、吉田健一
  • Journal Title: Am J Hum Genet Volume: 92 Issue: 3 Pages: 431-438
  • DOI: 10.1016/j.ajhg.2013.01.015
  • Peer Reviewed
• [Journal Article] Lenalidomide-induced acute lung injury in case of multiple myeloma. (2013)
  • Author(s): Danbara, M., Tadera, N., Togano, T., Katayama, T., Aoki, T., Miyazaki, K., Higashihara, M.
  • Journal Title: Int. J. Clin. Pharmacol. Ther Volume: 51(6) Issue: 06 Pages: 513-516
  • DOI: 10.5414/cp201840
  • Peer Reviewed
• [Journal Article] Incidence and clinical significance of abberrant T-cell marker expression on diffuse large B-cell lymphoma cells. (2013)
  • Author(s): Suzuki Y, Yoshida T, Wang G, Aoki T, Katayama T, Miyamoto S, Miyazaki K, Iwabuchi K, Danbara M, Nakayama M, Horie R, Nakamine H, Sato Y, Nakamura N, Niitsu N.
  • Journal Title: Acta Hematologica Volume: 130 Issue: 4 Pages: 230-237
  • DOI: 10.1159/000348550
  • Peer Reviewed
• [Journal Article] Fcγ receptor IIB gene polymorphism in adult Japanese patients with primary immune thrombocytopenia. (2013)
  • Author(s): Satoh T1, Miyazaki K, Shimohira A, Amano N, Okazaki Y, Nishimoto T, Akahoshi T, Munekata S, Kanoh Y, Ikeda Y, Higashihara M, Takahashi S, Kuwana M.
  • Journal Title: Blood Volume: Sep 12;122 Issue: 11 Pages: 1991-2
  • DOI: 10.1182/blood-2013-05-501858
  • Peer Reviewed
• [Journal Article] Surface CD3 expression proceeds through both myosin regulatory light chain9 (MYL9)-dependent and MYL9-independent pathways in Jurkat cells. (2012)
  • Author(s): Aoki T, Miyazaki K, Katayama T, Watanabe M, Horie R, Danbara M, Higashihara M.
  • Journal Title: Journal of Smooth Muscle Research Volume: 48 Pages: 137-147
  • NAID: 10031151480
  • Peer Reviewed
• [Presentation] Tail Mutation of MYH9 inhibits the disassembly of non-muscle myosin IIA (2015)
  • Author(s): Miyazaki K, Komatsu S, Jung HS, Higashihara M, Craig R, Ikebe M.
  • Organizer: 欧州血液学会
  • Place of Presentation: ウイーン（オーストリア）
  • Year and Date: 2015-06-11 – 2015-06-14
• [Presentation] Detection of Anti-Thrombopoietin Antibodies in Patients with Immune Thrombocytopenia (2014)
  • Author(s): Satoh T, Miyazaki K, Shimada N, Nagane K, Inukai T, Nakajima H, Higashihara M, Takahashi S.
  • Organizer: 米国血液学会
  • Place of Presentation: サンフランシスコ（アメリカ合衆国）
  • Year and Date: 2014-12-08
• [Presentation] Detection of Anti-Thrombopoetin Auto-antibody Among Immune Thrombocytopenic Patients (2014)
  • Author(s): Miyazaki K, Satoh T, Osawa E, Modegi N, Kita A, Kurihara S, Kawasaki Y, Kodaira Y, Shimada N, Nagane K, Takahashi S.
  • Organizer: 欧州血液学会
  • Place of Presentation: ミラノ（イタリア）
  • Year and Date: 2014-06-13
• [Presentation] 未熟血小板分画は巨大血小板減少症と特発性血小板減少性紫斑病との鑑別に 有用である (2013)
  • Author(s): 宮崎浩二
  • Organizer: 第３５回日本血栓止血学会
  • Place of Presentation: 山形市
• [Presentation] IMPAIRED PROPLATELET FORMATION IN A NOVEL GLANZMANN VARIANT MACROTHROMBOCYTOPENIA (2013)
  • Author(s): 宮崎浩二
  • Organizer: 第１８回欧州血液学会
  • Place of Presentation: スウェーデン、ストックホルム
• [Presentation] The Immature Platelet Fraction Is Susceptible To The Platelet Size And Useful For Screening Of Macrothrombocytopenia From Immune Thrombocytopenia (2013)
  • Author(s): 宮崎浩二
  • Organizer: 国際血栓止血学会総会(ISTH2013)
  • Place of Presentation: オランダ、アムステルダム
• [Presentation] The Immature Platelet Fraction Is Sensitive to the Platelet Size and a Useful Parameter for Screening for Macrothrombocytopenia (2012)
  • Author(s): 宮崎浩二
  • Organizer: 米国血液学会年次総会2012
  • Place of Presentation: アメリカ合衆国、アトランタ