Basic stydies of suppression to expansion of PNH colne by new methods

2012 Fiscal Year Final Research Report

• Project/Area Number: 22591044
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Fukushima Medical University
• Principal Investigator: SHICHISHIMA Tsutomu 福島県立医科大学, 医学部, 研究員 (10192105)
• Co-Investigator(Kenkyū-buntansha): SHIKAMA Yayoi 福島県立医科大学, 医学部, 准教授 (40291562) ; NOJI Hideyoshi 福島県立医科大学, 医学部, 講師 (20347214)
• Co-Investigator(Renkei-kenkyūsha): IKEDA Kazuhiko 福島県立医科大学, 医学部, 助教 (90381392) ; NASHIMOTO Masayuki 新潟薬科大学, 応用生物科学, 教授 (30228069)
• Project Period (FY): 2010 – 2012
• Keywords: 血液内科学

Research Abstract

We investigated telomere length, activity of teilmerase, and the regulation mechanisms in GPI+/GPI- cells from patients with paroxysmal nocturnal hemogolbinuria(PNH), so that the differences of hematopoietics in hemolytic PNH and bone-marrow-failure-type PNH are clarified. In addition, the mechanisms of expansion of PNH clones are also unclear, but WT1 and HMGA2 are thought to be associating with that. Then we also incestigated suppress effects for the sxpansions fo PNH clones by those genes, due to development of molecularly targeted therapy for PNH.

Research Products

• [Journal Article] Deregulated expression of HMGA2 is implicated in clonal expansion of PIGA deficient cells in paroxysmal nocturnal haemoglobinuria (2012)
  • Author(s): Murakami Y, Inoue N, Shichishima T, Ohta R, Noji H, Maeda Y, Nishimura J, Kanakura Y, Kinoshita T, haemoglobinuria D
  • Journal Title: BrJHaematol Volume: 156(3) Pages: 383-387
  • DOI: DOI:10.1111/j.1365-2141.2011.08914.x
• [Journal Article] Maturity-dependent fractionation of neutrophil progenitors: A new method to examine in vivo expression profiles of differentiation-regulating genes (2012)
  • Author(s): Hu H, Shikama Y, Shichishima T, Ikeda K, Akutsu K, Ono T, Kimura H, Ogawa K, Noji H, Takeishi Y, Kimura J
  • Journal Title: ExpHematol Volume: 40(8) Pages: 675-681
  • DOI: DOI:10.1016/j.exphem.2012.03.003
• [Journal Article] Safety and feasibility of high-dose ranimustine (MCNU), carboplatin, etoposide, and cyclophosphamide (MCVC) therapy followed by autologous stem cell transplantation for malignant lymphoma (2012)
  • Author(s): Kameoka Y, Takahashi N, Ishizawa K, Kato Y, Ito J, Sasaki O, Murai K, Noji H, Hirokawa M, Tajima K, Shichishima T, Ishida Y, Harigae H, Sawada K
  • Journal Title: Int J Hematol Volume: 96(5) Pages: 624-630
  • DOI: DOI:10.1007/s12185-012-1186-7
• [Journal Article] T-cell prolymphocytic leukemia in Japan: is it a variant (2012)
  • Author(s): Kameoka J, Takahashi N, Noji H, Murai K, Tajima K, Kameoka Y, Sato S, Shichishima T, Ishida Y, Harigae H, Sawada K
  • Journal Title: Int J Hematol Volume: 96(5) Pages: 660-667
  • DOI: DOI:10.1007/s12185-012-1077-y
• [Journal Article] A patient with acute lymphoblastic leukaemia presenting with an extremely high level (21.0%) of HbA1c (2011)
  • Author(s): Suzuki Y, Shichishima T, Yamashiro Y, Kimura H, Ishii R, Miyazaki K, Horie R, Moriya T, Hattori Y
  • Journal Title: Ann Clin Biochem Volume: 48(5) Pages: 474-477
  • DOI: DOI:10.1258/acb.2011.010121
• [Journal Article] Comparison of long-term clinical outcomes of CHOP chemotherapy between Japanese patients with nodal peripheral T-cell lymphomas and those with diffuse large B-cell lymphoma in the study group of the Tohoku Hematology Forum (2011)
  • Author(s): Akagi T, Takahashi N, Yamaguchi K, Ishizawa K, Murai K, Tajima K, Ikeda K, Kameoka Y, Kameoka J, Ito S, Kato Y, Noji H, Shichishima T, Itoh J, Ichinohasama R, Harigae H, Ishida Y, Sawada K
  • Journal Title: J Clin Exp Hematopathol Volume: 51(1) Pages: 29-35
  • DOI: DOI:10.3960/jslrt.51.29
• [Journal Article] Impairment of FOS mRNA induction by a translation inhibitor puromycin in granulocytes from myelodysplastic syndrome patients (2011)
  • Author(s): Shikama Y, XiaoMin F, Shichishima T, Ono T, Noji H, Ikeda K, Ogawa K, Takeishi Y, Kimura J
  • Journal Title: Br J haematol Volume: 154(4) Pages: 525-527
  • DOI: DOI:10.1111/j.1365-2141.2010.08504.x
• [Journal Article] Safety and efficacy of the terminal complement inhibitor eculizumab in Japanese patients with paroxysmal nocturnal hemoglobinuria: the AEGIS Clinical Trial (2011)
  • Author(s): Kanakura Y, Ohyashiki K, Shichishima T, Shinichiro O, Ando K, Ninomiya H, Kawaguchi T, Nakao S, Nakakuma H, Nishimura J, Kinoshita T, Bedrosian C, Valentine M, Khursigara G, Ozawa K, Omine M
  • Journal Title: Int J hematol Volume: 93(1) Pages: 36-46
  • DOI: DOI:10.1007/s12185-010-0748-9
• [Journal Article] 特集骨髄不全症診療の新しい展開PNHの病態解析と治療の進歩 (2011)
  • Author(s): 七島勉
  • Journal Title: 血液内科 Volume: 63(2) Pages: 208-215
• [Journal Article] Low concentration of serum haptoglobin has impact on understanding complex pathophysiology in patients with acquired bone marrow failure syndromes (2010)
  • Author(s): Shichishima T, Ikeda K, Takahashi N, Kameoka J, Tajima K, Murai K, Tamai Y, Shichishima-Nakamura A, Akutsu K, Noji H, Okamoto M, Kimura H, Harigae H, Oyamada T, Kamesaki T, Takeishi Y, Sawada K
  • Journal Title: Int J Hematol Volume: 91(4) Pages: 602-610
  • DOI: DOI:10.1007/s12185-010-0559-z
• [Journal Article] Transcripts expressed using a bicistronic vector pIREShyg2 are sensitized to nonsense-mediated mRNA decay (2010)
  • Author(s): Shikama Y, Hu H, Ohno M, Matsuoka I, Shichishima T, Kimura J
  • Journal Title: BMC Mol Biol Volume: 11 Pages: 42
  • DOI: DOI:10.1186/1471-2199-11-42
• [Journal Article] 解説:発作性夜間ヘモグロビン尿症の診断・治療の実際 (2010)
  • Author(s): 七島勉
  • Journal Title: 血液・腫瘍科 Volume: 60(6) Pages: 777-786
• [Presentation] Impairment of HuR-mediated FOS mRNA stabilization in granulocytes from myelodysplastic syndrome patients (2012)
  • Author(s): Xiaomin F, Yayoi S, Shichishima T, Noji H, Ikeda K, Ogawa K, Takeishi Y, Kimura J
  • Organizer: 2012 American Society of Hematology (ASH) Annual Meeting and Exposition
  • Place of Presentation: Atlanta, Georgia, USA
  • Year and Date: 20121208-11
• [Presentation] Morphologic and cytogenetic examinations with bone marrow cells in PNH patients (2012)
  • Author(s): Noji H, Hamanaka S, Yamaguchi K, Ogawa K, Murai K, Kimura H, Mita M, Suzuki I, Kohno K, Kimura S, Saitoh Y, Hatta S, Michishita Y, Kanbayashi H, Ishida Y, Harigae H, Sawada K, Takeishi Y, Shichishima T
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 20121019-21
• [Presentation] Detection of PNH-type cells using high-resolution flow cytometry: Interim analysis of OPTIMA study (2012)
  • Author(s): Hosokawa K, Sugimori C, Yamamoto M, Nishimura J, Yonemura Y, Obara N, Noji H, Nakamura Y, Ando K, Shichishima T, Ninomiya H, Chiba S, Kawaguchi T, Nakao S, Kanakura Y
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 20121019-21
• [Presentation] Mechanism of impaired FOS mRNA induction by emetine in myelodysplastic syndrome granulocytes. (2012)
  • Author(s): Feng X, Shikama Y, Noji H, Shichishima T, Ikeda K, Ogawa K, Takeishi Y, Kimura J
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 20121019-21
• [Presentation] A preliminary study on telomere length of granulocytes and mononuclear cells in PNH patients (2012)
  • Author(s): Takahashi H, Noji H, Takeishi Y, Shichishima T
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 20121019-21
• [Presentation] Erythema annulare centrifugum in a patient with paroxysmal nocturnal hemoglobinuria (2012)
  • Author(s): Noji H, Usuki K, Otsuka M, Horiuchi H, Yamamoto T, Takahashi H, Takeishi Y, Shichishima T
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 20121019-21
• [Presentation] Paroxysmal nocturnal hemoglobinuria in a patient with del(5q)(q23q32) myelodysplastic syndromes (2012)
  • Author(s): Mita M, Nakamura K, Takahashi H, Noji H, Takeishi Y, Shichishima T
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 20121019-21
• [Presentation] Del(13q) myelodysplastic syndromes in a patient with paroxysmal nocturnal hemoglobinuria (PNH) (2012)
  • Author(s): Kimura S, Saitou Y, Kanbayashi H, Matuda S, Odajima H, Takahashi H, Noji H, Takeishi Y, Shichishima T
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 20121019-21
• [Presentation] OPTIMA試験:高精度フローサイトメトリー法によるGPIアンカー膜蛋白欠損血球の検出 (2012)
  • Author(s): 山本正樹,西村純一,細川晃平,杉盛千春,米村雄士,小原直,中村嘉彦,野地秀義,七島勉,安藤潔,二宮治彦,千葉滋,川口辰哉,中尾眞二,金倉譲
  • Organizer: 第49回補体シンポジウム
  • Place of Presentation: 大阪
  • Year and Date: 20120824-25
• [Presentation] OPTIMA試験:高精度フローサイトメトリー法によるGPIアンカー型蛋白欠損血球の検出 (2012)
  • Author(s): 山本正樹, 西村純一, 細川晃平, 杉盛千春, 米村雄士, 小原 直, 野地秀義, 中村嘉彦, 安藤 潔, 七島 勉, 二宮治彦, 千葉 滋, 川口辰哉, 中尾眞二, 金倉 譲
  • Organizer: 第22回 サイトメトリー学会
  • Place of Presentation: 豊中
  • Year and Date: 20120629-30
• [Presentation] 特別講演:PNHの治療戦略とエクリズマブ.NPO法人 (2012)
  • Author(s): 七島勉
  • Organizer: PNH倶楽部設立1周年記念医療講演会
  • Place of Presentation: 東京
  • Year and Date: 2012-11-23
• [Presentation] 特別講演:最新のPNH治療 (2012)
  • Author(s): 七島勉
  • Organizer: 山形PNH講演会
  • Place of Presentation: 山形
  • Year and Date: 2012-09-21
• [Presentation] 特別講演:PNH治療の最新治験 (2012)
  • Author(s): 七島勉
  • Organizer: 秋田PNH講演会
  • Place of Presentation: 秋田
  • Year and Date: 2012-08-30
• [Presentation] 東北PNH 研究会: Paroxysmal nocturnal hemoglobinuria (PNH)症例におけるEculizumab治療の赤血球結合IgGおよびC3に対する影響 (2012)
  • Author(s): 野地秀義, 亀崎豊実, 濱中純子, 山口公平, 神林裕行, 竹石恭知, 七島勉
  • Organizer: 第4回造血器腫瘍免疫療法研究会
  • Place of Presentation: 金沢
  • Year and Date: 2012-08-18
• [Presentation] 骨髄低形成を伴うPNH 症例に対するEculizmab 使用経験. (2012)
  • Author(s): 野地秀義, 七島 勉, 竹石恭知
  • Organizer: 2012 Japan PNH Masters
  • Place of Presentation: 東京
  • Year and Date: 2012-07-28
• [Presentation] T-PIG研究の中間報告. (2012)
  • Author(s): 野地秀義, 七島 勉
  • Organizer: 第3回 東北PNH 研究会
  • Place of Presentation: 仙台
  • Year and Date: 2012-06-17
• [Presentation] 講演:PNH患者におけるエクリズマブ投与の実際 -自験例からの知見- (2012)
  • Author(s): 七島 勉
  • Organizer: 北海道PNH研究会
  • Place of Presentation: 札幌
  • Year and Date: 2012-01-20
• [Presentation] Long-term efficacy of Eculizumab in Japanese patients with PNH: AEGIS Trial. (2011)
  • Author(s): Gotoh A, Ohyashiki K, Kanakura Y, Okamoto S, Shichishima T, Ando K, Ninomiya H, Kawaguchi T, Nakao S, Nakakuma H, Nishimura J, Kinoshita T, Bedrosian C, Valentine M, Ozawa K, Omine M
  • Organizer: 第73回 日本血液学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 20111014-16
• [Presentation] Safety and feasibility of MEAM therapy followed by auto-HSCT for malignant lymphoma (2011)
  • Author(s): Kameoka Y, Takahashi N, Akagi T, Hiroshima Y, Yokoyama H, Murai K, Tajima K, Shichishima T, Ishida Y, Harigae H, Sawada K
  • Organizer: 第73回 日本血液学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 20111014-16
• [Presentation] PNH-type cells by flow cytometric methods with a monoclonal antibody and FLAER in BMFS patients (2011)
  • Author(s): Takahashi H, Shichishima T, Noji H, Ogawa K, Takeishi Y
  • Organizer: 第73回 日本血液学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 20111014-16
• [Presentation] Efficacy of Eculizumab for nontransfused Japanese patients with PNH: case report from AEGIS study (2011)
  • Author(s): Shirasugi Y, Ando K, Kanakura Y, Okamoto S, Ohyashiki K, Shichishima T, Ninomiya H, Kawaguchi T, Nakao S, Nakakuma H, Nishimura J, Kinoshita T, Bedrosian C, Valentine M, Ozawa K, Omine M
  • Organizer: 第73回 日本血液学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 20111014-16
• [Presentation] 補体研究:基礎から臨床へ:発作性夜間血色素尿症をはじめとするGPI欠損症について(シンポジウム) (2011)
  • Author(s): 村上良子, 井上徳光, 七島 勉, 太田里永子, 野地秀義, 前田裕輔, 西村純一, 木下タロウ
  • Organizer: 第48回 補体シンポジウム
  • Place of Presentation: 名古屋
  • Year and Date: 20110902-03
• [Presentation] Paroxysmal nocturnal hemoglobinuria (PNH) 8症例におけるEculizumabの効果および安全性 (2011)
  • Author(s): 野地秀義, 七島 勉, 高橋裕志, 小川一英, 竹石恭知
  • Organizer: 第3回 造血器腫瘍免疫療法研究会学術集会
  • Place of Presentation: 別府
  • Year and Date: 20110820-21
• [Presentation] 特別講演:PNHの多様性と治療戦略. NPO法人PNH倶楽部 (2011)
  • Author(s): 七島 勉
  • Organizer: 設立報告会・記念講演会
  • Place of Presentation: 東京
  • Year and Date: 2011-11-23
• [Presentation] 溶血を伴う骨髄不全型PNHに対するアプローチ:骨髄不全型PNHの自験例(パネルディスカッション) (2011)
  • Author(s): 七島 勉
  • Organizer: 第2回 北陸PNH研究会
  • Place of Presentation: 金沢
  • Year and Date: 2011-10-29
• [Presentation] 種々のPNH症例とその治療経験 (Hemorrhagic diathesis in PNH: A case of PNH complicating acquired von Willebrand disease (vWD) during clinical course) (2011)
  • Author(s): 七島 勉
  • Organizer: Japan PNH Masters Program
  • Place of Presentation: 東京
  • Year and Date: 2011-07-17
• [Presentation] Expression of HMGA2 in blood cells from patients with paroxysmal nocturnal hemoglobinuria (2010)
  • Author(s): Murakami Y, Inoue N, Shichishima T, Noji H, Nishimura J, Kanakura Y, Kinoshita T
  • Organizer: 52nd American Society of Hematology (ASH) Annual Meeting and Exposition
  • Place of Presentation: Orlando, FL, USA
  • Year and Date: 20101004-07
• [Presentation] Appearance of CD59-negative leukemic cells in patients with acute myeloid leukemia. (2010)
  • Author(s): 高橋裕志, 七島 勉, 野地秀義, 古川未希, 七島晶子, 竹石恭知
  • Organizer: 第72回 日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 20100924-26
• [Presentation] Studies on GPI-anchor expressions by flow cytometry using FLAER in patients with acquired BMFS (2010)
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 20100924-26
• [Presentation] Effect of long term eculizumab treatment on chronic kidney disease in Japanese patients with PNH (2010)
  • Author(s): Shichishima T, Kanakura Y, Ohyashiki K, Okamoto S, Ando K, Ninomiya H, Kawaguchi T, Nakao S, Nakakuma H, Nishimura J, Kinoshita T, Ozawa K, Omine M
  • Organizer: 第72回 日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 20100924-26
• [Presentation] Safety, feasibility and efficacy of MCVC therapy followed by auto-PBSCT for malignant lymphoma. (2010)
  • Author(s): Kameoka Y, Takahashi N, Hirokawa M, Aoki Y, Yamamoto J, Kato Y, Hiroshima Y, Ito J, Noji H, Ishizawa K, Shichishima T, Ishida Y, Harigae H, Sawada K
  • Organizer: 第72回 日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 20100924-26
• [Presentation] Impaired c-fos induction by emetin in granulocytes from myelodysplastic syndrome patients. (2010)
  • Author(s): Feng X, Shikama Y, Shichishima T, Noji H, Ogawa K, Takeishi Y
  • Organizer: 第72回 日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 20100924-26
• [Presentation] Two paroxysmal nocturnal hemoglobinuria patients reached hematological and clonal remission. (2010)
  • Organizer: 第72回 日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 20100924-26
• [Presentation] Clinical and biological features of T-cell prolymphocytic leukemia in Japan (2010)
  • Author(s): Kameoka J, Takahashi N, Noji H, Murai K, Tajima K, Kameoka Y, Shichishima T, Ishida Y, Harigae H, Sawada K
  • Organizer: 第72回 日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 20100924-26
• [Presentation] Analysis of autologous PBSCT in four patients with cardiac amyloidosis. (2010)
  • Author(s): Ogawa K, Kimura S, Furukawa M, Harada K, Mashimo Y, Takahashi H, Matsumoto H, Shichishima-Nakamura A, Ohkawara H, Noji H, Shichishima T, Ohto H, Takeishi Y
  • Organizer: 第72回 日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 20100924-26
• [Presentation] A PNH patient complained of MDS and developed AML (2010)
  • Organizer: 第72回 日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 20100924-26
• [Presentation] 講演:PNHにおける補体溶血と関連した病態(ランチョンセミナー). (2010)
  • Author(s): 七島 勉
  • Organizer: 第47回 補体シンポジウム
  • Place of Presentation: 福島
  • Year and Date: 20100910-11
• [Presentation] 発作性夜間ヘモグロビン尿症4症例におけるヒト化モノクローナル抗C5抗体 (Eculizumab) の効果および安全性の検討 (2010)
  • Author(s): 野地秀義, 七島 勉, 高橋裕志, 小川一英, 竹石恭知
  • Organizer: 第47回 補体シンポジウム
  • Place of Presentation: 福島
  • Year and Date: 20100910-11
• [Presentation] 発作性夜間ヘモグロビン尿症(PNH)4 症例におけるEculizumabの効果および安全性 (2010)
  • Author(s): 野地秀義, 七島 勉, 高橋裕志, 小川一英, 竹石恭知
  • Organizer: 第2回造血器腫瘍免疫療法研究会学術集会
  • Place of Presentation: 松山
  • Year and Date: 20100828-29
• [Presentation] PNH 診断と治療について(パネルディスカッション) (2010)
  • Author(s): 金倉 護, 西村純一, 中熊秀樹, 七島 勉, 二宮治彦, 川口辰哉
  • Organizer: 日本PNH研究会・関西キックオフミーティング
  • Place of Presentation: 大阪
  • Year and Date: 2010-10-09
• [Presentation] 講演:PNHと生きる (2010)
  • Author(s): 七島 勉
  • Organizer: ソリリス 発売記念講演会
  • Place of Presentation: 東京
  • Year and Date: 2010-08-28
• [Presentation] 急性骨髄性白血病(AML)症例におけるCD59陰性白血病細胞の出現
  • Author(s): 野地秀義, 七島 勉, 岡本正俊, 池田和彦, 七島晶子, 阿久津和子, 竹石恭知
• [Presentation] 後天性骨髄不全症候群(BMFS)症例におけるFLAERによるGPIアンカー発現の検討
  • Author(s): 高橋裕志, 七島 勉, 野地秀義, 古川未希, 七島晶子, 竹石恭知
• [Presentation] 血液学的およびクローン性寛解に至った発作性夜間ヘモグロビン尿症の2症例
  • Author(s): 古川未希, 野地秀義, 七島 勉, 原田佳代, 眞下由美子, 高橋裕志, 松本勇人, 木村 哲, 七島晶子, 大河原浩, 小川一英, 竹石恭知
• [Presentation] 急性骨髄性白血病へ移行した骨髄異形成症候群を合併した発作性夜間ヘモグロビン尿症の一例
  • Author(s): 木村 哲, 野地秀義, 七島 勉, 大河原浩, 古川未希, 原田佳代, 眞下由美子, 高橋裕志, 松本勇人, 七島晶子, 小川一英, 竹石恭知
• [Book] 病気と薬パーフェクトブック2011,発作性夜間ヘモグロビン尿症 (2011)
  • Author(s): 七島勉
  • Total Pages: 780-782
  • Publisher: 南山堂,東京
• [Book] 病気と薬パーフェクトブック2010,発作性夜間ヘモグロビン尿症 (2010)
  • Author(s): 七島勉
  • Total Pages: 732-733
  • Publisher: 南山堂,東京