Mechanisms for expression of antiapoptotic protein survivin in refractory childhood leukemia

• Project/Area Number: 18591201
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Dokkyo Medical University
• Principal Investigator: KUROSAWA Hidemitsu Dokkyo Medical University, 医学部, 准教授 (10205239)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,100,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥600,000); Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
• Keywords: E2A-HLF / t(17;19)ALL / survivin / AIF / caspase independent apoptosis / アポトーシス / 急性白血病 / t(17;:19) / apoptosis inducing factor / SURVIVIN / t(17:19)^+ALL / Apoptosis Inducing Factor / 急性リンパ性白血病 / SURIVIN / t(17;19)

Research Abstract

難治性17;19転座白血病(t(17;19)^+ALL)でアポトーシス抑制因子survivinが高発現している。このt(17;19)^+ALL におけるsurvivin発現機構とアポトーシス抑制機構について解析を実施した。siRNA法を用いたsurvivinのノックダウンではt(17;19)^+ALL特異的にアポトーシスが誘導できた。survivinはcaspase依存性と非依存性の坑アポトーシス抑制機構が存在する。t(17;19)^+ALLでは主に後者が関与していることを証明した。また、その主な作用機序としてAIFの核内移行の抑制を確認しているが、AIFをノックダウンするとsurvivin機能を抑制してもアポトーシスが抑制することを証明した。

Research Products

• [Journal Article] Hemostatic management of surgery for imperforate anus in a patient with 13q deletion syndrome with combined deficiency of factors VII and X (2009)
  • Author(s): Kurosawa H, Suzumura H, Okuya M, Fukushima K, Sugita K, Toshio F, Morishita E, Yoshioka A, Takamiya O, Arisaka O
  • Journal Title: Haemophilia 15 Pages: 398-400
  • Peer Reviewed
• [Journal Article] Chronic active Epstein -Barr virus infection with mosquito allergy successfully treated with reducedintensity unrelated allogeneic bone marrow transplantation in a boy (2009)
  • Author(s): Matsunaga T, Kurosawa H, Okuya M, Nakajima D, Hagisawa S, SatoY, Fukushima K, Sugita K, Arisaka O
  • Journal Title: Pediatric Transplantion 13 Pages: 231-234
  • Peer Reviewed
• [Journal Article] Hemostatic management of surgery for imperforate anus in a patient with 13q deletion syndrome with combined deficiency of factors VII and X. (2009)
  • Author(s): Hidemitsu Kurosawa, Hiroshi uzumura, et al.
  • Journal Title: Haemophilia 15 Pages: 398-400
  • Peer Reviewed
• [Journal Article] Chronic active Epstein-Barr virus infection with mosquito allergy successfully treated with reducedintensity unrelated allogeneic bone marrowtransplantation in a boy. (2009)
  • Author(s): Takayuki Matsunaga, KurosawaHidemitsu., et al.
  • Journal Title: Pediatric Transplantion 13 Pages: 231-234
  • Peer Reviewed
• [Journal Article] Oncogenic ras regulates survivin expression via mitogen-activated protein kinase and phosphatidylinositol-3 kinase in mouse interleukin-3 dependent hematopoietic Baf-3 cells (2008)
  • Author(s): Shinjyo T, Kurosawa H, Miyagi J, Ohama K, Masuda M, Matsui H, Inaba T, Furukawa Y, and Takasu N
  • Journal Title: Tohoku Journal of Experimental Medicine 216 Pages: 25-34
  • Peer Reviewed
• [Journal Article] A conditioning regimen of busulfan, fludarabine, and melphalan for allogeneic stem cell transplantation in children with juvenile myelomonocytic leukemia (2008)
  • Author(s): Yabe M, Sako M, Yabe H, Osugi Y, Kurosawa H, Nara T, Tokuyama M, Adachi S, Kobayashi C, Yanagimachi M, Ohtsuka Y, Nakazawa Y, Ogawa C, Atsushi M, Kojima S and Nakahata T for a Japanese Childhood MDS Study Group
  • Journal Title: Pediatric Transplantion 12 Pages: 862-867
  • Peer Reviewed
• [Journal Article] Oncogenic ras regulates survivin expression via mitogen-activated protein kinase and phosphatidylinositol-3 kinase in mouse interleukin-3 dependent hematopoietic Baf-3 cells. (2008)
  • Author(s): Tetsuharu Shinjyo, Hidemitsu Kurosawa, et al.
  • Journal Title: ohoku Journal of Experimental Medicine 216 Pages: 25-34
  • Peer Reviewed
• [Journal Article] Sever hyperbirilubinemia in a 10-year-old girl with combined disorder of hereditary spherocytosis syndrome (2007)
  • Author(s): Sugita K, Maruo Y, Kurosawa H, Tsuchioka A, Fujiwara T, Mori A, Ideguchi H, Eguchi M
  • Journal Title: Pediatr Int 49 Pages: 540-542
  • Peer Reviewed
• [Journal Article] Hypercalcemia in childhood acute lymphoblastic leukemia: frequent implication of parathyroid hormone-related peptide and E2A-HLF from translocation 17;19 (2007)
  • Author(s): Inukai T, Hirose K, Inaba T, Kurosawa H, Hama A, Inada H, Chin M, Nagatoshi Y, Ohtsuka Y, Oda M, H Goto H, Endo M, Morimoto A, Imaizumi M, Kawamura N, Miyajima Y, Ohtake M, Miyaji R, Saito M, Tawa A, Yanai F, Goi K, Nakazawa S, Sugita K
  • Journal Title: Leukemia 21 Pages: 288-296
  • Peer Reviewed
• [Journal Article] Successfully treated acute lymphoblastic leukemia associated with craniopharyngioma (2007)
  • Author(s): Kurosawa H, Matsunaga T, Shimura N, Nakajima D, Hagisawa S, Fukushima K, SugitaK, Kim P, Arisaka O
  • Journal Title: Journal of Pediatric Hematology/Oncology 29 Pages: 416-419
  • Peer Reviewed
• [Journal Article] Fetal hemophagocytic lymphohistiocytosis in a premature infant (2007)
  • Author(s): Nitta A, Suzumura H, Watabe Y, Okuya M, Nakajima D, Kurosawa H, Sugita K, Arisaka O
  • Journal Title: J Pediatr 151 Pages: 98-98
  • Peer Reviewed
• [Journal Article] Hypercalcemia in childhood acute lymphoblastic leukemia:frequent implication of parathyroid hormone-related peptide and E2-HLF from translocation 17;19 (2007)
  • Author(s): T lnukai, K Hirose, T lnaba, H Kurosawa, et. al.
  • Journal Title: Leukemia 21 Pages: 288-296
  • Peer Reviewed
• [Journal Article] Successfully treated acute lymphoblastic leukemia associated with craniopharyngioma (2007)
  • Author(s): H Kurosawa, T Matsunaga, et. al.
  • Journal Title: Journal of Pediatric Hematology/Oncology 29 Pages: 416-419
  • Peer Reviewed
• [Journal Article] Sever hyperbirilubinemia in a 10-year-old girl with combined disorder of hereditary spherocytosis syndrome (2007)
  • Author(s): K Sugita, Maruo Y, Kurosawa H, et. al.
  • Journal Title: Pediatric International 49 Pages: 540-542
  • Peer Reviewed
• [Journal Article] Fetal hemophagocytic lymphohistiocytosis in a premabue infant (2007)
  • Author(s): A Nitta, H Kurosawa, et. al.
  • Journal Title: Journal of Pediatrics 151 Pages: 98-98
  • Peer Reviewed
• [Journal Article] 小児白血病化学療法時の深在性真菌症に対するvoliconazoelによる治療-投与量と血中濃度の検討 (2007)
  • Author(s): 福島 啓太郎, 黒澤 秀光, 他
  • Journal Title: 日本臨床血液学会雑誌 48 Pages: 402-406
  • Peer Reviewed
• [Journal Article] Hypercalcemia in childhood acute lymphoblastic leukemia : frequent implication of parathyroid hormone-related peptide and E2A-HLF from translocation 17;19. (2007)
  • Author(s): T Inukai, K Hirose, T Inaba, H Kurosawa, et al.
  • Journal Title: Leukemia 7 Pages: 288-296
• [Journal Article] 緑膿菌敗血症で発症した好中球減少を伴うX連鎖性無γグロブリン血症の1例 (2006)
  • Author(s): 松永貴之, 山本詩子, 宮本健志, 黒沢秀光, 他。
  • Journal Title: 日本小児血液学会誌 20 Pages: 101-104
• [Journal Article] Kidd式(JKa)不適合妊娠による新生児溶血性疾患の1例 (2006)
  • Author(s): 松永貴之, 渡部功之, 山本詩子, 黒沢秀光, 他。
  • Journal Title: 小児科臨床 59 Pages: 1782-1794
• [Journal Article] Chronic active Epstein-Barr virus infection with dilatation of the Valsalva sinus (2006)
  • Author(s): Y Sato, T Tsuboi, T Mikami, H Kurosawa, et al.
  • Journal Title: Pediatric Internatiomal 48 Pages: 643-645
  • NAID: 10019261272
• [Journal Article] Peripheral Blood CD25+CD4+T cell in Childhood Patients Treated with Allogeneic Stem Cell Transplantation (2006)
  • Author(s): K Sugita, T Tsuboi, Y Sato, H Kurosawa
  • Journal Title: Recent Advances Research Update 7 Pages: 249-257
• [Presentation] 17:19転座型ALLにおけるcaspase非依存性細胞死の抑制 (2008)
  • Author(s): 黒澤秀光, 他
  • Organizer: 第70回日本血液学会
  • Place of Presentation: 国立京都国際会館・京都
  • Year and Date: 2008-10-11
• [Presentation] 高カルシウム血症を合併した急性リンパ性白血病における17:19転座のスクリーニング (2008)
  • Author(s): 犬飼岳史、滝智彦、小野厚、西村慎一郎、渡辺輝浩、小川淳、塩崎順子、康勝好、黒澤秀光、稲葉俊哉、広瀬衣子、黒田格、合井久美子、加賀美恵子、杉田莞爾
  • Organizer: 第50回日本小児血液学会
  • Place of Presentation: 幕張
• [Presentation] 17;19転座型ALLにおけるcaspase非依存性細胞死抑制 (2008)
  • Author(s): 黒澤秀光、奥谷真由子、菊地次郎、古川雄祐、犬飼岳史、安芸大輔、松井啓隆、稲葉俊哉、松下卓、佐藤雄也、萩澤進、福島啓太郎、杉田憲一、有阪治
  • Organizer: 第70回日本血液学会
  • Place of Presentation: 京都
• [Presentation] Induction of Death Receptors for TRAIL, a Cytotoxic Factor for GVL Effect, by Oncogenic Fusion E2A-HLF Derived from t(17;19)-Positive Acute Lymphoblastic Leukemia (2007)
  • Author(s): Zhang X, Inukai T, Akahane K, Hirose K, Kuroda I, Honna H, Goi K, Kagami K, Inaba T, Kurosawa H, Goto H, Endo M, Yagita H, A. T Look, Sugita K
  • Organizer: ASH meeting
  • Place of Presentation: Atlanta
• [Presentation] 17;19転座ALLの高カルシウム血症はE2A-HLFのよるPTHrPの発現誘導による (2007)
  • Author(s): 黒澤秀光、松永貴之、奥谷真由子、福島啓太郎、杉田憲一、犬飼岳史、稲葉俊哉、遠藤幹也、後藤裕明、有阪治
  • Organizer: 第69回日本血液学会・第49回日本臨床血液学会合同総会
  • Place of Presentation: 横浜
• [Presentation] 17;19転座型球性リンパ性白血病の臨床像 (2007)
  • Author(s): 犬飼岳史、永利義久、大塚欣敏、稲田浩子、後藤裕明、遠藤幹也、中村こずえ、黒澤秀光、稲葉俊哉、廣瀬衣子、合井久美子、杉田完爾
  • Organizer: 第49回日本小児血液学会・第23回日本小児がん学会学術集会
  • Place of Presentation: 仙台
• [Presentation] Induction of death receptors for TRAIL,a cytotoxic factor for GVL effect,by oncogenic fusion E2A-HLF derived from t(17;19)-positive acute lymphoblastic leukemia (2007)
  • Author(s): X Zhang, T Inukai, H Kurosawa, et. al.
  • Organizer: The American Sociaty of Hematology.49thAnnual meeting
  • Place of Presentation: Atlanta,USA
• [Presentation] 17;19転座型ALLにおけるLMO2の過剰発現と細胞死の抑制作用 (2007)
  • Author(s): 廣瀬 衣子, 犬飼 岳史, 黒澤 秀光, 他
  • Organizer: 第69回日本血液学会・第49回日本臨床血液学会合同総会
  • Place of Presentation: 横浜
• [Presentation] IX因子複合製剤輸注下に鎖肛の手術を施行した13q-症候群 (2007)
  • Author(s): 黒澤 秀光, 鈴村 宏, 他
  • Organizer: 第49回日本小児血液学会・第23回日本小児がん学会学術集会
  • Place of Presentation: 仙台