Exploration for therapeutic target using a novel prognostic factor IKZF1 targeting cells in childhood acute lymphoblastic leukemia

• Project/Area Number: 24591568
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: National Hospital Organization Nagoya Medical Center
• Principal Investigator: HATTORI Hiroyoshi 独立行政法人国立病院機構(名古屋医療センター臨床研究センター), その他部局等, その他 (20624513)
• Co-Investigator(Kenkyū-buntansha): HORIBE Keizo 独立行政法人国立病院機構名古屋医療センター, 臨床研究センター, 臨床研究センター長 (30209308)
• Research Collaborator: SAITO Yuko ; YAMASHITA Yuka
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 小児急性リンパ性白血病 / 抗がん剤感受性 / 予後因子 / BCP-ALLモデル細胞

Outline of Final Research Achievements

Patients with childhood acute lymphoblastic leukemia (ALL) in high risk recur about 30%. Recently, IKZF1 alteration in genomic DNA has been found as a prognostic factor. To elucidate the role of the IKZF1 alteration, we developed childhood ALL model cells with IKZF1 mutations. We investigated the relationship between the IKZF1 alteration and anti-cancer drug sensitivity which are frequently used in childhood ALL. The results showed the sensitivity to the several drugs may be dependent on the IKZF1 alteration.

Research Products

• [Journal Article] Dynamic modulation of thymidylate synthase gene expression and fluorouracil sensitivity in human colorectal cancer cells. (2015)
  • Author(s): Wakasa K, Kawabata R, Nakao S, Hattori H, Taguchi K, Uchida J, Yamanaka T, Maehara Y, Fukushima M, Oda S.
  • Journal Title: PLOS ONE Volume: 10
  • DOI: 10.1371/journal.pone.0123076
  • Peer Reviewed / Open Access
• [Journal Article] NF-kB signaling mediates acquired resistance after PARP inhibition. (2015)
  • Author(s): Nakagawa Y, Sedukhina AS, Okamoto N, Nagasawa S, Suzuki N, Ohta T, Hattori H, Roche-Molina M, Narváez AJ, Jeyasekharan AD, Bernal JA, Sato K.
  • Journal Title: Oncotarget Volume: 6 Pages: 3825-39
  • Peer Reviewed / Open Access
• [Journal Article] p53 shapes genome-wide and cell type-specific changes in microRNA expression during the human DNA damage response. (2014)
  • Author(s): Hattori H, Janky R, Nietfeld W, Aerts S, Babu MM, Venkitaraman AR.
  • Journal Title: Cell Cycle Volume: 13 Pages: 2572-86
  • DOI: 10.4161/15384101.2015.942209
  • Peer Reviewed / Open Access
• [Journal Article] Nilotinib monotherapy induced complete remission in pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia resistant to imatinib and dasatinib. (2013)
  • Author(s): Sekimizu M, Yamashita Y, Ueki H, Akita N, Hattori H, Maeda N, Horibe K.
  • Journal Title: Leuk Lymphoma Volume: Epub ahead of print Pages: 1-2
  • Peer Reviewed
• [Journal Article] A cancer-associated BRCA2 mutation reveals masked nuclear export signals controlling localization. (2013)
  • Author(s): Jeyasekharan AD, Liu Y, Hattori H, Pisupati V, Jonsdottir AB, Rajendra E, Lee M, Sundaramoorthy E, Schlachter S, Kaminski CF, Ofir-Rosenfeld Y, Sato K, Savill J, Ayoub N, Venkitaraman AR.
  • Journal Title: Nat Struct Mol Biol. Volume: 20 Pages: 1191-8
  • DOI: 10.1038/nsmb.2666
  • Peer Reviewed
• [Journal Article] A-type lamins maintain the positional stability of DNA damage repair foci in mammalian nuclei. (2013)
  • Author(s): Mahen R, Hattori H, Lee M, Sharma P, Jeyasekharan AD, Venkitaraman AR.
  • Journal Title: PLoS One Volume: 8
  • DOI: 10.1371/journal.pone.0061893
  • Peer Reviewed
• [Journal Article] A DNA-damage selective role for BRCA1 E3 ligase in claspin ubiquitylation, CHK1 activation, and DNA repair. (2012)
  • Author(s): Sato K, Sundaramoorthy E, Rajendra E, Hattori H, Jeyasekharan AD, Ayoub N, Schiess R, Aebersold R, Nishikawa H, Sedukhina AS, Wada H, Ohta T, Venkitaraman AR
  • Journal Title: Curr Biol. Volume: 22 Pages: 1659-66
  • DOI: 10.1016/j.cub.2012.07.034
  • Peer Reviewed
• [Presentation] Clinical Issues for the Treatment of Adolescents and Young Adults with Hematologic Malignancy and Bone and Soft Tissue Sarcoma in Japan – A Single Institute’s Experience (2015)
  • Author(s): Hattori Hiroyoshi
  • Organizer: 9th St. Jude-VIVA Forum in Pediatric Oncology
  • Place of Presentation: Singapore
  • Year and Date: 2015-03-28 – 2015-03-29