The role of the AEP complex in MLL fusion-dependent leukemogenesis

• Project/Area Number: 23689050
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Hematology
• Research Institution: Kyoto University
• Principal Investigator: YOKOYAMA Akihiko 京都大学, 医学(系)研究科(研究院), 准教授 (10506710)
• Research Collaborator: OKUDA Hiroshi 京都大学, 医学研究科, 特定助教 (10629215)
• Project Period (FY): 2011-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥24,830,000 (Direct Cost: ¥19,100,000、Indirect Cost: ¥5,730,000); Fiscal Year 2014: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2013: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2012: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2011: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: 白血病 / MLL / 転写 / AF4 / 癌 / 発現制御 / 生体分子 / 内科 / 蛋白質 / エピジェネティクス / がん

Outline of Final Research Achievements

Cancer threatens the lives of many people. Even the young generation including infants suffers from leukemia. One of the major causes of infant leukemia is the mutation of the MLL gene. The prognosis of this type of leukemia is unfavorable in the current regimens. We aim to develop new therapeutic strategies for this leukemia by deciphering the mechanisms of the genesis of leukemia. In this research, we unveiled the mechanisms by which MLL mutants cause hyper activation of their target genes. We showed that MLL mutants first associate with a transcriptional regulatory factor called AEP and then recruit other regulatory factors to activate gene expression to cause leukemia.

Research Products

• [Journal Article] Molecular mechanisms of MLL-associated leukemia. (2015)
  • Author(s): Yokoyama, A.
  • Journal Title: International journal of hematology Volume: 101 Issue: 4 Pages: 352-361
  • DOI: 10.1007/s12185-015-1774-4
  • Peer Reviewed
• [Journal Article] MLL fusion proteins link transcriptional coactivators to previously active CpG-rich promoters (2014)
  • Author(s): Okuda H, Kawaguchi M, Kanai A, Matsui H, Kawamura T, Inaba T, Kitabayashi I, Yokoyama A
  • Journal Title: Nucleic Acid Research Volume: 未定 Issue: 7 Pages: 1-16
  • DOI: 10.1093/nar/gkt1394
  • NAID: 120005439160
  • Peer Reviewed
• [Journal Article] Cleary ML MLL becomes functional through intra-molecular interaction not by proteolytic processing. (2013)
  • Author(s): Yokoyama A, Ficara F, Murphy M, Meisel C, Hatanaka C, Kitabayashi I,
  • Journal Title: PLOS ONE Volume: 8(9) Issue: 9 Pages: e73649-e73649
  • DOI: 10.1371/journal.pone.0073649
  • Peer Reviewed
• [Journal Article] Molecular mechanisms of leukemogenesis in MLL-leukemias (2011)
  • Author(s): Yokoyama A
  • Journal Title: Rinsho Ketsueki Volume: 52(8) Pages: 679-685
  • NAID: 10029615131
  • Peer Reviewed
• [Presentation] Reading epigenetic marks and activating transcription by MLL fusion proteins (2014)
  • Author(s): Akihiko Yokoyama
  • Organizer: 9th 3R symposium
  • Place of Presentation: 御殿場
  • Year and Date: 2014-11-17 – 2014-11-21
  • Invited
• [Presentation] Mechanisms of aberrant self-renewal caused by MLL fusion oncoproteins (2014)
  • Author(s): Akihiko Yokoyama
  • Organizer: 4th Global Cancer Genomics Consortium
  • Place of Presentation: 京都
  • Year and Date: 2014-11-14 – 2014-11-15
  • Invited
• [Presentation] The molecular mechanisms of MLL fusion-dependent leukemic transformation (2014)
  • Author(s): Akihiko Yokoyama
  • Organizer: 5th JSH International Symposium
  • Place of Presentation: 浜松
  • Year and Date: 2014-05-24 – 2014-05-25
  • Invited
• [Presentation] MLL白血病の分子メカニズム (2013)
  • Author(s): 横山明彦
  • Organizer: 第７回先進血液学レクチャー
  • Place of Presentation: 東京都、東京ドームホテル
  • Invited
• [Presentation] Molecular mechanism of MLL-associated leukemia (2013)
  • Author(s): 横山明彦
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 神奈川県、パシフィコ横浜
  • Invited
• [Presentation] Molecular mechanism of MLL fusion-dependent transformation (2013)
  • Author(s): 横山 明彦
  • Organizer: 日米造血器腫瘍セミナー
  • Place of Presentation: Makena Beach and Golf Resort, Maui, Hawaii、USA
  • Invited
• [Presentation] MLL白血病の発症メカニズム (2012)
  • Author(s): 横山明彦
  • Organizer: 平成23年度第3次対がん10か年総合戦略(平成16年~25年度)・文部科学省がん研究分野の特性等を踏まえた支援活動合同公開シンポジウム
  • Place of Presentation: 東京都(学術総合センター一橋記念講堂)(招待講演)
• [Presentation] MLL白血病と転写制御
  • Author(s): 横山 明彦
  • Organizer: 三重先端がんフォーラム
  • Place of Presentation: 三重大学
  • Invited
• [Remarks] 大日本住友製薬 京都大学 (DSK) 連携プロジェクト 悪性制御研究ラボ
  • URL: http://www.dsk.med.kyoto-u.ac.jp