Novel therapeutic strategy on analysis of molecular mechanism through micro RNA in refractory leukemia

• Project/Area Number: 21790911
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Hematology
• Research Institution: Mie University
• Principal Investigator: ONO Ryoichi 三重大学, 大学院・医学系研究科, 講師 (40422414)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 造血器腫瘍 / マイクロRNA / MLL / 白血病 / micro RNA

Research Abstract

In the present study, I first developed a model of refractory leukemic cells with rearrangement of chromosome 11q23 as previously described, and characterized this model cells. On the basis of characterization, comprehensive analysis of total RNA derived these cells revealed interesting deviation of at least three kinds of micro RNA expression. This finding was confirmed by other experiments. To examine the possibility of clinical benefit on this finding, I am investigating a novel vector transducing micro RNA expression, and also going to analyze therapeutic effect using this vector.

Research Products

• [Journal Article] IKAROS isoform 6 enhances BCR-ABL1-mediated proliferation of human CD34+ hematopoietic cells on stromal cells (2012)
  • Author(s): Suzuki K, Ono R, Ohishi K, Masuya M, Kataoka I, Liu B, Nakamori Y, Ino K, Monma F, Hamada H, Kitamura T, Katayama N, Nosaka T
  • Journal Title: Int J Oncol Volume: 40 Pages: 53-62
  • Peer Reviewed
• [Journal Article] MLL融合遺伝子による白血病発症機構 (2010)
  • Author(s): 野阪哲哉、小埜良一
  • Journal Title: 血液・腫瘍科 Volume: 61 Pages: 217-223
  • NAID: 40019064212
• [Journal Article] Expression of ADAMTS4 in Ewing's sarcoma (2010)
  • Author(s): Minobe K, Ono R, Matsumine A, Shibata-Minoshima F, Izawa K, Oki T, Kitaura J, Iino T, Takita J, Iwamoto S, Hori H, Komada Y, Uchida A, Hayashi Y, Kitamura T, Nosaka T
  • Journal Title: Int J Oncol Volume: 37 Pages: 569-581
  • Peer Reviewed
• [Journal Article] Expression of ADAMTS4 in Ewing's sarcoma. (2010)
  • Author(s): Minobe K, Ono R, et al.
  • Journal Title: International Journal of Oncology Volume: 37 Pages: 569-581
  • Peer Reviewed
• [Journal Article] Mixed-lineage-leukemia(MLL) fusion protein collaborates with Ras to induce acute leukemia through aberrant Hox expression and Raf activation (2009)
  • Author(s): Ono R, Kumagai H, Nakajima H, Hishiya A, Taki T, Horikawa K, Takatsu K, Satoh T, Hayashi Y, Kitamura T, Nosaka T
  • Journal Title: Leukemia Volume: 23 Pages: 2197-2209
  • Peer Reviewed
• [Journal Article] FLT3-ITD induces ara-C resistance in myeloid leukemic cells through the repression of the ENT1 expression (2009)
  • Author(s): Jin G, Matsushita H, Asai S, Tsukamoto H, Ono R, Nosaka T, Yahata T, Takahashi S, Miyachi H
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 390 Pages: 1001-1006
  • Peer Reviewed
• [Journal Article] Possible involvement of RasGRP4 in leukemogenesis (2009)
  • Author(s): Watanabe-Okochi N, Oki T, Komeno Y, Kato N, Yuji K, Ono R, Harada Y, Harada H, Hayashi Y, Nakajima H, Nosaka T, Kitaura J, Kitamura T
  • Journal Title: Int J Hematol Volume: 89 Pages: 470-481
  • Peer Reviewed
• [Journal Article] Mixed-lineage-leukemia (MLL) fusion protein collaborates with Ras to induce acute leukemia through aberrant Hox expression and Raf activation (2009)
  • Author(s): Ono RR, et al.
  • Journal Title: Leukemia 23 Pages: 2197-2209
  • Peer Reviewed
• [Journal Article] FLT3-ITD induces ara-C resistance in myeloid leukemic cells through the repression of the ENT1 expression. (2009)
  • Author(s): Jin G, Matsushita H, Asai S, Tsukamoto H, Ono R, et al.
  • Journal Title: Biochemical and Biophysical Research Communications 390 Pages: 1001-1006
  • Peer Reviewed
• [Journal Article] Possible involvement of RasGRP4 in leukemogenesis. (2009)
  • Author(s): Watanabe-Okochi N, Oki T, Komeno Y, Kato N, Yuji K, Ono R, et al.
  • Journal Title: International Journal of Hematology 89 Pages: 470-481
  • Peer Reviewed
• [Presentation] 11q23転座型白血病における自己複製能関連転写因子を介した新規分子メカニズムの解析 (2011)
  • Author(s): 小埜良一、桝屋正浩、中島秀明、榎本豊、宮田恵里、上迫努、伊藤守、中村彰秀、鈴木圭、片山直之、北村俊雄、野阪哲哉
  • Organizer: 第53回日本小児血液・がん学会学術集会
  • Place of Presentation: 前橋
  • Year and Date: 2011-11-25
• [Presentation] Ewing肉腫における新規腫瘍マーカーの探索: ADAMTS4発現の診断的意義の解析 (2011)
  • Author(s): 美濃部こころ、松峯昭彦、小埜良一、飯野隆大、林泰秀、北村俊雄、内田淳正、須藤啓広、野阪哲也
  • Organizer: 第26回日本整形外科学会基礎学術集会
  • Place of Presentation: 前橋
  • Year and Date: 2011-10-20
• [Presentation] Ewing肉腫における新規腫瘍マーカーの探索:ADAMTS4発現の診断的意義の解析 (2011)
  • Author(s): 美濃部こころ、松峯昭彦、小埜良一, ら
  • Organizer: 第26回日本整形外科学会基礎学術集会
  • Place of Presentation: 前橋
  • Year and Date: 2011-10-20
• [Presentation] MLL融合遺伝子による白血病発症における自己複製能関連転写因子を介した新規分子機構の解析 (2011)
  • Author(s): 小埜良一、桝屋正浩、中島秀明、榎本豊、宮田恵里、上迫努、伊藤守、中村彰秀、鈴木圭、片山直之、北村俊雄、野阪哲哉
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-15
• [Presentation] Differential role of PU. 1 in leukemogenesis by Hoxa9-Meis1 or MLL-fusion oncogene (2011)
  • Author(s): Fukuchi Y, Sadahira K, Kunimoto H, Sakurai M, Masuda A, Kawakita J, Ono R, Kitamura T, Nosaka T, Okamoto S, Nakajima H
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-15
• [Presentation] Differential role of PU.1 in leukemogenesis by Hoxa9-Meis1 or MLL-fusion oncogene (2011)
  • Author(s): Fukuchi Y, Sadahira K, Kunimoto H, Sakurai M, Masuda A, Kawakita J, Ono R, et al
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-15
• [Presentation] ifferential role of myeloid transcription factors, C/EBPa and PU. 1 in leukemogenesis by MLL-fusion oncogenes (2010)
  • Author(s): Fukuchi Y, Kuroda K, Sadahira K, Ono R, Tenen DG, Kitamura T, Nosaka T, Okamaoto S, Nakajima H
  • Organizer: 第52回アメリカ血液学会
  • Place of Presentation: 米国フロリダ州オーランド
  • Year and Date: 2010-12-04
• [Presentation] Ikaros isoform 6 enhances proliferative effect by BCR-ABL1 in human CD34+ hematopoietic cells (2010)
  • Author(s): Suzuki K, Ono R, Ohishi K, Kataoka I, Masuya M, Hamada, Kitamura T, Katayama N, Nosaka T
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-26
• [Presentation] Ikaros isoform 6 (IK6) enhances proliferative effect by BCR-ABL1 inhuman CD34+ hematopoietic cells. (2010)
  • Author(s): Suzuki K, Ono R, et al.
  • Organizer: 日本血液学会
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-26
• [Presentation] Differential role of C/EBPαand PU. 1 in leukemogenesis by MLL-fusion oncogenes (2010)
  • Author(s): Fukuchi Y, Kuroda K, Sadahira K, Ono R, Ikeda Y, Kitamura T, Nosaka T, Okamaoto S, Nakajima H
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-24
• [Presentation] Differential role of C/EBPa and PU.1 in leukemogenesis by MLL-fusion oncogenes. (2010)
  • Author(s): Fukuchi Y, Kuroda K, Sadahira K, Ono R, et al.
  • Organizer: 日本血液学会
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-24
• [Presentation] Analysis of novel molecular mechanism in transformation by MLL-ENL targeting long-term hematopoietic stem cells (2010)
  • Author(s): Ono R, Masuya M, Nakajima H, Enomoto Y, Miyata E, Kamisako T, Ito M, Suzuki K, Katayama N, Kitamura T, Nosaka T
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-22
• [Presentation] Analysis of novel molecular mechanism in transformation by MLL-ENL targeting long-term hematopoietic stem cells (2010)
  • Author(s): Ono R, et al.
  • Organizer: 日本癌学会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-22
• [Presentation] MLL-ENL融合遺伝子は造血幹細胞のみを標的として形質転換を生じる (2009)
  • Author(s): 小埜良一,桝屋正浩,宮田恵里,中島秀明,上迫努,伊藤守,鈴木圭,片山直之,北村俊雄,野阪哲哉
  • Organizer: 第71回日本血液学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2009-10-24
• [Presentation] MLL-ENL融合遺伝子は造血幹細胞のみを標的として形質転換を生じる (2009)
  • Author(s): 小埜良一, ら
  • Organizer: 日本血液学会
  • Place of Presentation: 京都
  • Year and Date: 2009-10-24
• [Presentation] Malignant transformation by MLL-ENL fusion gene arises selectively from long-term hematopoietic stem cells (2009)
  • Author(s): Ono R, Masuya M, Miyata E, Nakajima H, Kamisako T, Ito M, Suzuki K, Katayama N, Kitamura T, Nosaka T
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-01
• [Presentation] MLL-ENL融合遺伝子による形質転換は造血幹細胞のみを標的として生じる (2009)
  • Author(s): 小埜良一, ら
  • Organizer: 日本癌学会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-01
• [Remarks]
  • URL: http://www.medic.mie-u.ac.jp/microbiol/
• [Remarks]
  • URL: http://www.medic.mie-u.ac.jp/microbiol/