Molecular mechanism of MLL-related leukemogenesis in a mouse modelfor generation of cancer stem cells

2012 Fiscal Year Final Research Report

• Project/Area Number: 22390206
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Mie University
• Principal Investigator: NOSAKA Tetsuya 三重大学, 大学院・医学系研究科, 教授 (30218309)
• Co-Investigator(Kenkyū-buntansha): KITAMURA Toshio 東京大学, 医科学研究所, 教授 (20282527) ; ONO Ryoichi 三重大学, 大学院・医学系研究科, 講師 (40422414)
• Project Period (FY): 2010 – 2012
• Keywords: 小児血液学 / 白血病幹細胞 / 白血病モデルマウス / MLL / 乳児白血病

Research Abstract

We developed a transgenic mouse conditionally expressing an MLL chimeric gene which is frequently found in infantile and childfood leukemia patients. In this model system, leukemic stem cells were found to derive from only a hematopoieticstem cell population inducibly expressing MLL-ENL. PLZF gene was shown to play a pivotal role in development of MLL-ENL-mediated stem cell leukemia.

Research Products

• [Journal Article] Regulation of AMP-activated Protein Kinase Signaling by AFF4, a Member of the AF4 (ALL1-fused Gene from Chromosome 4) Family of Transcription Factors, in Hypothalamic Neurons (2012)
  • Author(s): Komori T, Doi A, Nosaka T, Furuta H, Akamizu T, Kitamura T, Senba E, Morikawa Y.
  • Journal Title: J Biol Chem Volume: 287 Pages: 19985-19996
  • DOI: DOI:10.1074/jbc.M112.367854
  • Peer Reviewed
• [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
  • DOI: DOI:10.3892/ijo.2011.1192
  • Peer Reviewed
• [Journal Article] 血液腫瘍モデル動物の現状と展望. In: 金倉譲 編集. 造血器腫瘍学-基礎と臨床の最新研究動向- (2012)
  • Author(s): 野阪哲哉
  • Journal Title: 日本臨床 Volume: 70 Suppl 2 Pages: 159-164
• [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] 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(2) Pages: 217-223
  • Peer Reviewed
• [Journal Article] Plzf drives MLL-fusion-mediated leukemogenesis specifically in long term hematopoietic stem cells
  • Author(s): Ono R, Masuya M, Nakajima H, Enomoto Y, Miyata E, Nakamura A, Ishii S, Suzuki K, Shibata-Minoshima F, Katayama N, Kitamura T, Nosaka T
  • Journal Title: Blood
  • Peer Reviewed
• [Journal Article] Manipulation of human early T lymphopoiesis by coculture on human bone marrow stromal cells: Potential utility for adoptive immunotherapy
  • Author(s): Liu B, Ohishi K, Orito Y,N a k a mo r i Y, Nishikawa H, Ino K,Suzuki K, Matsumoto T,Masuya M,Hamada H, Mineno J, Ono R, Nosaka T, Shiku H, Katayama N.
  • Journal Title: Exp Hematol
  • DOI: DOI:10.1016/j.exphem.2012.12.001
  • Peer Reviewed
• [Presentation] MLL fusion genes transform hematopoietic stem cells through an aberrant self-renewal program by Plzf (2012)
  • Author(s): Ono R, Masuya M, Nakajima H, Enomoto Y, Miyata E, Nakamura A, Ishii S, SuzukiK, Katayama N, Kitamura T, Nosaka T.
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2012-10-19
• [Presentation] Novel molecular mechanism of MLL-mediated leukemogenesis via a self-renewal transcription factor. (2011)
  • Author(s): Ono R, Masuya M, Nakajima H, Enomoto Y, Miyata E, Kamisako T, Ito M, NakamuraA, Suzuki K, Katayama N, Kitamura T, Nosaka T
  • 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, Okamaoto 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 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, KitamuraT, Nosaka T, Okamaoto S, Nakajima H
  • Organizer: 第52回アメリカ血液学会
  • Place of Presentation: Orlando, FL, USA
  • 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, HamadaH, 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] 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
• [Remarks] 三重大学大学院 医学系研究科 感染症制御医学・分子遺伝学分野 ホームページ
  • URL: http://www.medic.mie-u.ac.jp/microbiol/