Analysis of leukemogenic mechanisms by deregulated histone methylation

• Project/Area Number: 25830081
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Hiroshima University
• Principal Investigator: YAMASAKI Norimasa 広島大学, 技術センター, 技術主任 (70564136)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: ヒストン脱メチル化酵素 / Fbxl10 / トランスジェニックマウス / 造血幹細胞

Outline of Final Research Achievements

I found that overexpression of Fbxl10, a histone demethylase, in hematopoietic stem cells induced leukemia. To elucidate the underlying molecular mechanisms, I isolated Fbxl10-overexpressing hematopoietic stem cell and performed RNA-seq analysis. I found the enhanced expression patterns of neuron specific gene 2 (Nsg2) that is implicated in intracellular transport, and genes involved in oxidative phosphorylation. In addition, by ChIP analysis, I confirmed that these genes are direct targets of Fbxl10. These results provide novel insights into the leukemogenic mechanisms from the viewpoint of intracellular transport and oxidative phosphorylation.

Research Products

• [Journal Article] Fbxl10 overexpression in murine hematopoietic stem cells induces leukemia involving metabolic activation and up regulation of Nsg2. (2015)
  • Author(s): Ueda T, Nagamachi A, Takubo K, Yamasaki N, Matsui H, Kanai A, Nakata Y, Ikeda K, Konuma T, Oda H, Wolff L, Honda ZI, Wu X, Helin K, Iwama A, Suda T, Inaba T, Honda H.
  • Journal Title: Blood Volume: 125
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Acquired deficiency of A20 results in rapid apoptosis, systemic inflammation, and abnormal hematopoietic stem cell function. (2014)
  • Author(s): Nagamachi A, Nakata Y, Ueda T, Yamasaki N, Ebihara Y, Tsuji K, Honda Zi, Takubo K, Suda T, Oda H, Inaba T, Honda H.
  • Journal Title: PLOS ONE. Volume: 9(1)
  • Peer Reviewed
• [Journal Article] CIZ1, a p21Cip/Waf1-interacting protein, function as a tumor suppressor in vivo. (2013)
  • Author(s): Nishibe R, Watanabe W, Ueda T, Yamasaki N, Koller R, Wolff L, Honda Zi, Ohtsubo M, Honda H.
  • Journal Title: FEBS Letters. Volume: 587(10) Pages: 1529-1535
  • Peer Reviewed
• [Remarks] 広島大学 原爆放射線医科学研究所 疾患モデル解析研究分野ホームページ
  • URL: http://home.hiroshima-u.ac.jp/sosai/top.html