Analysis of EVI1-expressing leukemia using inv(3)(q21;q26) model mice

2013 Fiscal Year Final Research Report

• Project/Area Number: 24790957
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Tohoku University
• Principal Investigator: SUZUKI Mikiko 東北大学, 医学(系)研究科(研究院), 講師 (80508309)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 白血病 / EVI1 / 染色体転座 / 染色体逆位 / エンハンサー / GATA2 / 大腸菌人工染色体 / トランスジェニックマウス

Research Abstract

Chromosomal translocation and inversion between 3q21 and 3q26 result in misexpression of EVI1 gene on 3q26, which induces leukemogenesis with poor diagnosis. To examine the underlying mechanism of leukemogenesis, we generated a novel mouse model of EVI1-expressing leukemia (3q21q26 mice) harboring a transgene recapitulating the inverted allele by linking two bacterial artificial chromosome (BAC) clones. The 3q21q26 mice suffer from myeloid and lymphoid leukemia after 24 weeks of age. We discovered an abnormal CD34-high cell fraction specifically in the bone marrow of 3q21q26 mice, suggesting that these cells are associated with leukemia.

Research Products

• [Journal Article] A remote GATA2 hematopoietic enhancer drives leukemogenesis in inv(3)(q21;q26) by activating EVI1 expression (2014)
  • Author(s): Yamazaki H, SuzukiM, Otsuki A, Shimizu R, Bresnick EH, Engel JD, and Yamamoto M
  • Journal Title: Cancer Cell Volume: 25 Pages: 415-427
  • DOI: 10.1016/j.ccr.2014.02.008
  • Peer Reviewed
• [Journal Article] The Gata15' region harbors distinct cis-regulatory modules that direct gene activation in erythroid cells and gene inactivation in HSCs (2013)
  • Author(s): Takai J, Moriguchi T, S u z u k i M , Yu L, Ohneda K, and Yamamoto M
  • Journal Title: Blood Volume: 122 Pages: 3450-3460
  • DOI: 10.1182/blood-2013-01-476911
  • Peer Reviewed
• [Journal Article] GATA factor switching from GATA2 to GATA1 contributes to erythroid differentiation (2013)
  • Author(s): Suzuki M , Kobayashi-Osaki M, Tsutsumi S, Pan X, Ohmori S, Takai J, Moriguchi T, Ohneda O, Ohneda K, Shimizu R, Kanki Y, Kodama T, Aburatani H, and Yamamoto M
  • Journal Title: Genes Cells Volume: 18 Pages: 921-933
  • DOI: 10.1111/gtc.12086
  • Peer Reviewed
• [Journal Article] Establishment of erythroleukemic GAK14 cells and characterization of GATA1 N-terminal domain (2013)
  • Author(s): Mukai HY, Suzuki M , Nagano M, Ohmori S, Otsuki A, Tsuchida K, Moriguchi T, Ohneda K, Shimizu R, Ohneda O, and Yamamoto M
  • Journal Title: Genes Cells Volume: 18 Pages: 886-898
  • DOI: 10.1111/gtc.12084
  • Peer Reviewed
• [Journal Article] Naturally occurring oncogenic GATA1 mutants with internal deletions in transient abnormal myelopoiesis in Down syndrome (2013)
  • Author(s): Toki T, Kanezaki R, Kobayashi E, Kaneko H, Suzuki M , Wang R, Terui K, Kanegane H, Maeda M, Endo M, Mizuochi T, Adachi S, Hayashi Y, Yamamoto M, Shimizu R, and Ito E
  • Journal Title: Blood Volume: 121 Pages: 3181-3184
  • DOI: 10.1182/blood-2012-01-405746
  • Peer Reviewed
• [Journal Article] Hereditary persistence of fetal hemoglobin is associated with disruption of the HBS1L-MYB locus (2013)
  • Author(s): Suzuki M , Yamazaki H, Mukai HY, Motohashi H, Shi L, Tanabe O, Engel JD, and Yamamoto M
  • Journal Title: Mol Cel lBiol Volume: 33 Pages: 1687-1695
  • DOI: 10.1128/MCB.01617-12
  • Peer Reviewed
• [Journal Article] The regulation of GATA factor expression is distinct between erythroid and mast cell lineages (2012)
  • Author(s): Ohmori S, Takai J, Ishijima Y, S u z u k i M , Moriguchi T, Philipsen S, Yamamoto M, and Ohneda K
  • Journal Title: Mol Cell Biol Volume: 32 Pages: 4742-4755
  • DOI: 10.1128/MCB.00718-12
  • Peer Reviewed
• [Presentation] 染色体転座・逆位によるEVI1 発現白血病の新規マウスモデル樹立とEVI1 遺伝子発現制御解析 (2014)
  • Author(s): 鈴木未来子, 山㟢博未, 大槻晃史, 清水律子, Emery H. Bresnick, James Douglas Engel, 山本雅之
  • Organizer: 平成25年度「個体レベルでのがん研究支援活動」ワークショップ個体レベルからみた炎症とがん
  • Place of Presentation: 琵琶湖ホテル, 滋賀
  • Year and Date: 20140217-18
• [Presentation] GATA2 遺伝子エンハンサーがinv(3)(q21;q26)においてEVI1 遺伝子を活性化し白血病を誘発する (2014)
  • Author(s): 鈴木未来子, 山㟢博未, 大槻晃史, 清水律子, Emery H. Bresnick, James Douglas Engel, 山本雅之
  • Organizer: 第18回造血器腫瘍研究会
  • Place of Presentation: がん研究会がん研究所, 東京
  • Year and Date: 2014-02-07
• [Presentation] 白血病逆位モデルマウスを用いたEVI1 高発現白血病発症機構の解析 (2013)
  • Author(s): 鈴木未来子, 山㟢博未, 加藤幸一郎, 清水律子, James Douglas Engel, 山本雅之
  • Organizer: 第17回造血器腫瘍研究会
  • Place of Presentation: 宮崎
  • Year and Date: 20130201-02
• [Presentation] 3q21q26 白血病染色体転座・逆位モデルマウスを用いたEVI1 遺伝子転写活性化機構の解析 (2013)
  • Author(s): 鈴木未来子, 山㟢博未, 加藤幸一郎, 清水律子, James Douglas Engel, 山本雅之
  • Organizer: 転写研究会若手ワークショップ@鬼怒川
  • Place of Presentation: 鬼怒川
  • Year and Date: 20130124-26
• [Presentation] 大腸菌人工染色体(BAC)を用いた3q21q26 染色体転座・逆位によるEVI1 遺伝子高発現白血病モデルマウスの樹立 (2012)
  • Author(s): 鈴木未来子, 山㟢博未, 清水律子, James Douglas Engel, 山本雅之
  • Organizer: 日本生化学会東北支部第78回例会・シンポジウム
  • Place of Presentation: 山形
  • Year and Date: 2012-05-26
• [Remarks] 研究内容紹介
  • URL: http://www.dmbc.med.tohoku.ac.jp/cgi-bin/project/view.cgi
• [Remarks] プレスリリース(2014年4月4日)「染色体転座・逆位による白血病発症機構を解明」
  • URL: http://www.med.tohoku.ac.jp/news/2441.html
• [Remarks] 河北新報(2014年4月4日)「白血病発症, DNA 領域の一部が鍵に東北大などが解明」
  • URL: http://www.kahoku.co.jp/tohokunews/201404/20140404_13006.html