The mechanism of polycythemia vera and essential thrombocythemia

• Project/Area Number: 20591137
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: University of Miyazaki
• Principal Investigator: SHIMODA Kazuya University of Miyazaki, 医学部, 教授 (90311844)
• Co-Investigator(Kenkyū-buntansha): SHIDE Kotaro 宮崎大学, 医学部, 研究員 (20468028)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 血液内科学 / 血液腫瘍学 / 原発性骨髄線維症 / 真性多血症 / 本態性血小板血症 / JAK2

Research Abstract

The expression level of mutant JAK2 would determine the cell lineage to grow, as higher expression of mutant JAK2 would favor erythrocytosis, and low JAK2 expression would favor thrombocytosis in mutant JAK2 transgenic mice.

Research Products

• [Journal Article] Tyrosine kinase 2 interacts with the proapoptotic protein Siva-1 and augments its apoptotic functions. (2010)
  • Author(s): Shimoda HK, Shide K, Kameda T, Matsunaga T, Shimoda K
  • Journal Title: Biochem Biophys Res Commun. 400 Pages: 252-257
  • Peer Reviewed
• [Journal Article] Absence of gain-of-function JAK1 and JAK3 mutations in adult T cell leukemia/lymphoma. (2010)
  • Author(s): Kameda T, Shide K, Shimoda HK, Hidaka T, Kubuki Y, Katayose K, Taniguchi Y, Sekine M, Kamiunntenn A, Maeda K, Nagata K, Matsunaga T, Shimoda K
  • Journal Title: Int J Hematol 92 Pages: 320-325
  • Peer Reviewed
• [Journal Article] JAK2 V617F uses distinct signalling pathways to induce cell proliferation and neutrophil activation. (2010)
  • Author(s): Oku S, Takenaka K, Kuriyama T, Shide K, Kumano T, Kikushige Y, Urata S, Yamauchi T, Iwamoto C, Shimoda HK, Miyamoto T, Nagafuji K, Kishimoto J, Shimoda K, Akashi K.
  • Journal Title: Br J Haematol. 150 Pages: 334-344
  • Peer Reviewed
• [Journal Article] p27 deregulation by Skp2 overexpression induced by the JAK2V617 mutation. (2010)
  • Author(s): Furuhata A, Kimura A, Shide K, Shimoda K, Murakami M, Ito H, Gao S, Yoshida K, Tagawa Y, Hagiwara K, Takagi A, Kojima T, Suzuki M, Abe A Naoe T, Murate T
  • Journal Title: Biochem Biophys Res Commun. 383 Pages: 411-416
  • Peer Reviewed
• [Journal Article] Prognostic impact of immunohistochemical biomarkers in diffuse large B-cell lymphoma in the rituximab era. (2010)
  • Author(s): Seki R, Ohshima K, Fujisaki T, Uike N, Kawano F, Gondo H, Makino S, Eto T, Moriuchi Y, Taguchi F, Kamimura T, Tsuda H, Ogawa R, Shimoda K, Yamashita K, Suzuki K, Suzushima H, Tsukazaki K, Higuchi M, Utsunomiya A, Iwahashi M, Imamura Y, Tamura K, Suzumiya J, Yoshida M, Abe Y, Matsumoto T, Okamura T
  • Journal Title: Cancer Science 100 Pages: 1842-1847
  • NAID: 10027195531
  • Peer Reviewed
• [Journal Article] Tyrosine kinase 2 interacts with the proapoptotic protein Siva-1 and augments its apoptotic functions. (2010)
  • Author(s): Shimoda HK, Shide K, Kameda T, Matsunaga T, Shimoda K
  • Journal Title: Biochem Biophys Res Commun. Volume: 400 Pages: 252-257
  • Peer Reviewed
• [Journal Article] Absence of gain-of-function JAK1 and JAK3 mutations in adult T cell leukemia/lymphoma. (2010)
  • Author(s): Kameda T, Shide K, Shimoda HK, Hidaka T, Kubuki Y, Katayose K, Taniguchi Y, Sekine M, Kamiunntenn A, Maeda K, Nagata K, Matsunaga T, Shimoda K.
  • Journal Title: Int J Hematol. Volume: 92 Pages: 320-325
  • Peer Reviewed
• [Journal Article] JAK2 V617F uses distinct signalling pathways to induce cell proliferation and neutrophil activation. (2010)
  • Author(s): Oku S, Takenaka K, Kuriyama T, Shide K, Kumano T, Kikushige Y, Urata S, Yamauchi T, Iwamoto C, Shimoda HK, Miyamoto T, Nagafuji K, Kishimoto J, Shimoda K, Akashi K.
  • Journal Title: Br J Haematol. Volume: 150 Pages: 334-344
  • Peer Reviewed
• [Journal Article] VLA-5-mediated adhesion to fibronectin accelerates hemin-stimulated erythroid differentiation of K562 cells through induction of VLA-4 expression. (2009)
  • Author(s): Tanaka R, Owaki T, Kamiya S, Matsunaga T, Shimoda K, Kodama H, Hayashi R, Abe T, Harada YP, Shimonaka M, Yamaji H, Terada H, Fukai F
  • Journal Title: J.Biol.Chem. 284 Pages: 19817-19825
  • Peer Reviewed
• [Journal Article] The impact of cytogenetic abnormalities on the prognosis of primary myelofibrosis : a prospective survey of 202 cases in Japan. (2009)
  • Author(s): Hidaka T, Shide K, Shimoda H, Kameda T, Toyama K, Katayose K, Kubuki Y, Nagata K, Takenaka K, Akashi K, Okamura T, Niho Y, Mizoguchi H, Omine M, Ozawa K, Harada M, Shimoda K
  • Journal Title: Eur J Haematol. 83 Pages: 328-333
  • Peer Reviewed
• [Journal Article] p27 deregulation by Skp2 overexpression induced by the JAK2V617 mutation (2009)
  • Author(s): Furuhata A, Shimoda K, et al.
  • Journal Title: Biochem Biophys Res Commun 383 Pages: 411-416
  • Peer Reviewed
• [Journal Article] VLA-5-mediated adhesion to fibronectin accelerates hemin-stimulated erythroid differentiation of K562 cells, through induction of VLA-4 expression (2009)
  • Author(s): Tanaka R, Shimoda K, et al.
  • Journal Title: J Biol Chem 284 Pages: 19817-19825
  • Peer Reviewed
• [Journal Article] Prognostic impact of immunohistochemical biomarkers in diffuse large B-cell lymphoma in the rituximab era (2009)
  • Author(s): Seki R, Shimoda K, et al.
  • Journal Title: Cancer Science 100 Pages: 1842-1847
  • NAID: 10027195531
  • Peer Reviewed
• [Journal Article] The impact of cytogenetic abnormalities on the prognosis of primary myelofibrosis : a prospective survey of 202 cases in Japan (2009)
  • Author(s): Hidaka T, Shimoda K, et al.
  • Journal Title: Eur J Haematol 83 Pages: 328-333
  • Peer Reviewed
• [Journal Article] Development of ET, primary myelofibrosis, and PV in mice expressing JAK2 V617F. (2008)
  • Author(s): Shide K,ShimodaHK, Kumano T, Karube K, KamedaT, Takenaka K, Abe H, Oku S, Katayose K K, Kusumoto K, Hasuike S, Tahara Y, Nagata K, Matsuda T, Ohshima K, Hrada M, Shimoda K
  • Journal Title: Leukemia 22 Pages: 87-89
  • NAID: 120007123093
  • Peer Reviewed
• [Journal Article] Endoscopic characterization of the small bowel in patients with portal hypertension evaluated by double balloon endoscopy. (2008)
  • Author(s): Kodama M,UtoH,Numata M, Hori T, Murayama T, Sasaki F, Tsubouchi N, IdoA, Shimoda K, Tsubouchi H.
  • Journal Title: J.Gastroenterol. 43 Pages: 589-596
  • NAID: 10021937551
  • Peer Reviewed
• [Journal Article] Tyk2-signaling plays an important role in host defense against Escherichia coli through IL-23-induced IL-17 production by gammadelta T cells. (2008)
  • Author(s): Nakamura R, Shibata K, Yamada H, Shimoda K, Nakayama K, Yoshikai Y.
  • Journal Title: J.Immunol. 181 Pages: 2071-2075
  • Peer Reviewed
• [Journal Article] Development of ET, primary myelofibrosis, and PV in miceexpressing JAK2 V617F. (2008)
  • Author(s): Shide K, ShimodaH K, Kumano T, Karube K, KamedaT, Takenaka K, Abe H, Oku S, Katayose K K, Kusumoto K, Hasuike S, Tahara Y, Nagata K, Matsuda T, Ohshima K, Hrada M, Shimoda K
  • Journal Title: Leukemia 22 Pages: 87-89
  • NAID: 120007123093
  • Peer Reviewed
• [Journal Article] Endoscopic characterization of the small bowel in patients with portal hypertension evaluated by double balloon endoscopy. (2008)
  • Author(s): Kodama M, UtoH, Numata M, Hori T, Murayama T, Sasaki F, Tsubouchi N, Ido A, Shimoda K, Tsubouchi H.
  • Journal Title: J. Gastroenterol. 43 Pages: 589-596
  • NAID: 10021937551
  • Peer Reviewed
• [Journal Article] Tyk2-signaling plays an important role in host defence against Escherichia coli through IL-23-induced IL-17 production by gammadelta T cells. (2008)
  • Author(s): Nakamura R, Shibata K, Yamada H, Shimoda K, Nakayama K, Yoshikai Y
  • Journal Title: J. Immunol. 181 Pages: 2071-2075
  • Peer Reviewed
• [Presentation] Prognostic impact of cytogenetic abnormalities in primary myelofibrosis : prospective survey in Japan. (2010)
  • Author(s): Shide K, Matsunaga T, Takenaka K, Hidaka T, Shimoda H, Kameda T, Katayose K, Kubuki Y, Akashi K, Okamura T, Niho Y, Mizoguchi H, Omine M, Ozawa K, Harada M, Shimoda K.
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2010-09-26
• [Presentation] Elevated neutrophil alkaline phosphatase scores induced by Jak2 V617F mutation via Stat3 (2009)
  • Author(s): Oku S, Shimoda K, Katsuto T, Kumano T, Kuriyama T, Urata S, Yamauchi T, Shide K, Shimoda H, Miyamoto T, Shimoda K, Akashi K.
  • Organizer: 第71回日本血液学会学術集会
  • Place of Presentation: 京都府京都市
  • Year and Date: 2009-10-24
• [Presentation] 新規JAK2阻害剤R723は、骨髄増殖疾患モデルマウスの病態を改善する (2009)
  • Author(s): 幣光太郎、亀田拓郎、Markobtsov Vadim、下田晴子、下田和哉, 他
  • Organizer: 第71回日本血液学会学術集会
  • Place of Presentation: 京都府京都市
  • Year and Date: 2009-10-24
• [Presentation] 成人T細胞性白血病/リンパ腫におけるJAK1遺伝子変異の検討 (2009)
  • Author(s): 亀田拓郎、幣光太郎、下田晴子、日高智徳、下田和哉, 他
  • Organizer: 第71回日本血液学会学術集会
  • Place of Presentation: 京都府京都市
  • Year and Date: 2009-10-24
• [Presentation] Elevated neutrophil alkaline phosphatase scores induced by Jak2 V617F mutation via Stat3 (2009)
  • Author(s): Oku S, Shimoda K, et al
  • Organizer: 第71回日本血液学会学術集会
  • Place of Presentation: 国立京都国際会館(京都)
  • Year and Date: 2009-10-24
• [Presentation] The animal model for myelofibrosis (2008)
  • Author(s): 下田晴子
  • Organizer: The 32nd World Congress of the International Society of Hematology
  • Place of Presentation: Thailand
  • Year and Date: 2008-10-23
• [Presentation] JAK2 V617F発現マウスは真性多血症、本態性血小板増多症、原発性骨髄線維症を発症する (2008)
  • Author(s): 幣光太郎、下田晴子、加留部謙之輔、熊野孝、亀田拓郎、下田和哉, 他
  • Organizer: 第70日本血液学会総会
  • Place of Presentation: 京都府京都市
  • Year and Date: 2008-10-11
• [Book] 今日の治療指針 2011年版 (慢性リンパ性白血病chronic lymphocytic leukemia(CLL)) (2011)
  • Author(s): 下田和哉
  • Publisher: 医学書院
• [Book] WHO血液腫瘍分類～WHO分類2008をうまく活用するために～(骨髄増殖性腫瘍7.肥満細胞症) (2010)
  • Author(s): 下田晴子、下田和哉
  • Publisher: 医薬ジャーナル社
• [Book] WHO血液腫瘍分類～WHO分類2008をうまく活用するために～(骨髄増殖性腫瘍4.原発性骨髄線維症 Primary myelofibrosis) (2010)
  • Author(s): 幣光太郎、下田和哉
  • Publisher: 医薬ジャーナル社
• [Book] WHO血液腫瘍分類～WHO分類2008をうまく活用するために～(骨髄増殖性腫瘍4.骨髄増殖性腫瘍、分類不能型Myeloproliferative neoplasma, unclassifiable) (2010)
  • Author(s): 久冨木庸子、下田和哉
  • Publisher: 医薬ジャーナル社
• [Book] 今日の診断指針原発性骨髄線維症 (2010)
  • Author(s): 下田和哉
  • Publisher: 医学書院
• [Book] 血液疾患最新の治療2011-2013(骨髄増殖性腫瘍) (2010)
  • Author(s): 松永卓也、下田和哉
  • Publisher: 南江堂
• [Book] 造血器腫瘍治療 これは困ったぞ、どうしよう!(52歳の骨髄線維証.移植,摘脾,治療方針は?) (2010)
  • Author(s): 松永卓也、下田和哉
  • Publisher: 中外医学社
• [Book] ガイドラインパースペクティブ(造血幹細胞移植骨髄増殖性疾患) (2009)
  • Author(s): 幣光太郎、下田和哉
  • Publisher: (株)医薬ジャーナル社
• [Book] 臨床に直結する血液疾患診療のエビデンス骨髄増殖性疾患におけるJAK2遺伝子変異解析の臨床的意義は? (2009)
  • Author(s): 亀田拓郎、下田和哉
  • Publisher: 文光堂
• [Book] 内科学書(骨髄線維症) (2009)
  • Author(s): 下田和哉
  • Publisher: 中山書店
• [Book] 血液疾患診療ハンドブック(-診療の手引きと臨床データ集改訂版原発性骨髄線維症) (2009)
  • Author(s): 下田和哉、原田実根
  • Publisher: 医薬ジャーナル社
• [Book] 新臨床腫瘍学(改訂第2版)(がん薬物療法専門医のために慢性骨髄性白血病・骨髄増殖性腫瘍) (2009)
  • Author(s): 下田和哉
  • Publisher: (株)南江堂
• [Book] 血液診療エキスパート 白血病慢性骨髄増殖性疾患((真性多血症、本態性血小板血症、原発性骨髄線維症)の病態と治療) (2009)
  • Author(s): 日高智徳、下田和哉
  • Publisher: 中外医学社
• [Book] 今日の治療指針2008年版(真性多血症、本態性血小板血症、慢性特発性骨髄線維症) (2008)
  • Author(s): 下田和哉
  • Publisher: 医学書院
• [Book] Annual Review血液(2008真性多血症における新たなJAK2の遺伝子変異) (2008)
  • Author(s): 幣光太郎、下田和哉
  • Publisher: 中外医学社
• [Remarks] ホームページ等