A novel oncogenic function of Wilms tumor gene WT1 in leukemia

• Project/Area Number: 15K09476
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Osaka University
• Principal Investigator: Oji Yusuke 大阪大学, 医学系研究科, 教授 (20294100)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: WT1 / leukemia / 白血病 / 分子標的治療法

Outline of Final Research Achievements

In the present study, we showed that 1) WT1 protein, which is overexpressed in leukemia and various types of solid cancers, associated with metabolic enzymes in leukemia cells and 2) a small molecule targeting this association efficiently induced cell death in WT1-expressing leukemia cells. These results indicate that the association between WT1 protein and metabolic enzymes could be a novel target of molecule-targeted cancer therapy.

Research Products

• [Int'l Joint Research] アントワープ大学(ベルギー)
• [Journal Article] WT1 peptide-based immunotherapy for advanced thymic epithelial malignancies (2018)
  • Author(s): Oji Y、Inoue M、Takeda Y、Hosen N、Shintani Y、Kawakami M、Harada T、Murakami Y、Iwai M、Fukuda M、Nishida S、Nakata J、Nakae Y、Takashima S、Shirakata T、Nakajima H、Hasegawa K、Kida H、Kijima T、Morimoto S、Fujiki F、Tsuboi A、Morii E、Morita S、Sakamoto J、Kumanogoh A、Oka Y、Okumura M、Sugiyama H
  • Journal Title: International Journal of Cancer Volume: 142 Issue: 11 Pages: 2375-2382
  • DOI: 10.1002/ijc.31253
  • Peer Reviewed / Open Access
• [Journal Article] Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia (2017)
  • Author(s): Anguille Sebastien、et al
  • Journal Title: Blood Volume: 130 Issue: 15 Pages: 1713-1721
  • DOI: 10.1182/blood-2017-04-780155
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Wilms tumour 1 peptide vaccine as a cure-oriented post-chemotherapy strategy for patients with acute myeloid leukaemia at high risk of relapse. (2017)
  • Author(s): Nakata J, Nakae Y, Kawakami M, Morimoto S, Motooka D, Hosen N, Fujiki F, Nakajima H, Hasegawa K, Nishida S, Tsuboi A, Oji Y, Oka Y, Kumanogoh A, Sugiyama H.
  • Journal Title: Br J Haematol. Volume: XX Issue: 2 Pages: 287-290
  • DOI: 10.1111/bjh.14768
  • Peer Reviewed / Open Access
• [Journal Article] Association of WT1 IgG antibody against WT1 peptide with prolonged survival in glioblastoma multiforme patients vaccinated with WT1 peptide. (2016)
  • Author(s): Oji Y, Hashimoto N, Tsuboi A, Murakami Y, Iwai M, Kagawa N, Chiba Y, Izumoto S, Elisseeva O, Ichinohasama R, Sakamoto J, Morita S, Nakajima H, Takashima S, Nakae Y, Nakata J, Kawakami M, Nishida S, Hosen N, Fujiki F, Morimoto S, Adachi M, Iwamoto M, Oka Y, Yoshimine T, Sugiyama H.
  • Journal Title: Int J Cancer. Volume: 139 Issue: 6 Pages: 1391-401
  • DOI: 10.1002/ijc.30182
  • Peer Reviewed / Open Access
• [Journal Article] Syndecan-4 as a biomarker to predict clinical outcome for glioblastoma multiforme treated with WT1 peptide vaccine. (2016)
  • Author(s): Takashima S, Oka Y, Fujiki F, Morimoto S, Nakajima H, Nakae Y, Nakata J, Nishida S, Hosen N, Tatsumi N, Mizuguchi K, Hashimoto N, Oji Y, Tsuboi A, Kumanogoh A, Sugiyama H.
  • Journal Title: Future Sci OA Volume: 2
• [Journal Article] A Zbtb7a proto-oncogene as a novel target for miR-125a. (2016)
  • Author(s): Hojo N, Tatsumi N, Moriguchi N, Matsumura A, Morimoto S, Nakata J, Fujiki F, Nishida S, Nakajima H, Tsuboi A, Oka Y, Hosen N, Hayashi S, Sugiyama H, Oji Y.
  • Journal Title: Molecular Carcinogenesis Volume: - Issue: 12 Pages: 1-9
  • DOI: 10.1002/mc.22446
  • Peer Reviewed / Open Access
• [Journal Article] Identification of a Novel C-Terminal Truncated WT1 Isoform with Antagonistic Effects against Major WT1 Isoforms. (2015)
  • Author(s): Tatsumi N, Hojo N, Sakamoto H, Inaba R, Moriguchi N, Matsuno K, Fukuda M, Matsumura A, Hayashi S, Morimoto S, Nakata J, Fujiki F, Nishida S, Nakajima H, Tsuboi A, Oka Y, Hosen N, Sugiyama H, Oji Y.
  • Journal Title: PLoS One Volume: 10 Issue: 6 Pages: e0130578-e0130578
  • DOI: 10.1371/journal.pone.0130578
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Wilms' tumor gene WT1 promotes homologous recombination- mediated DNA damage repair (2015)
  • Author(s): Oji Y, Kobayashi J, et al.
  • Journal Title: Mol Carcinog Volume: in press Issue: 12 Pages: 1758-71
  • DOI: 10.1002/mc.22248
  • Peer Reviewed / Open Access
• [Journal Article] osen N, Sugiyama H, Oji Y. Deficiency in WT1-targeting microRNA-125a leads to myeloid malignancies and urogenital abnormalities. (2015)
  • Author(s): Tatsumi N, Hojo N, Yamada O, Ogawa M, Katsura Y, Kawata S, Morii E, Sakamoto H, Inaba R, Tsuda A, Fukuda I, Moriguchi N, Hasuwa H, Okabe M, Fujiki F, Nishida S, Nakajima H, Tsuboi A, Oka Y, Hosen N, Sugiyama H, Oji Y.
  • Journal Title: Oncogene Volume: 35 Issue: 8 Pages: 1003-14
  • DOI: 10.1038/onc.2015.154
  • Peer Reviewed / Acknowledgement Compliant