Development of therapeutic approach targeting DNA damage check point

• Project/Area Number: 23390271
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: SHUKI Mizutani 東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (60126175)
• Co-Investigator(Kenkyū-buntansha): TAKAGI Masatoshi 東京医科歯科大学, 大学院・医歯学総合研究科, 講師 (10406267)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥19,500,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥4,500,000); Fiscal Year 2013: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2012: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2011: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
• Keywords: 小児血液学 / DNA損傷応答 / ATM / BCR/ABL / microRNA / 細胞分化

Research Abstract

Development of therapeutic approach targeting DNA damage check point was investigated. loss of function of ATM was identified in neuroblastoma. It is known that ATM regulated microRNA and contributes down regulation of MYCN. We have identified several microRNAs regulated by ATM. Contribution of loss of ATM function in blastic crisis in chronic myelogenous leukemia was elucidated.

Research Products

• [Journal Article] ATM-dependent DNA damage-response pathway as a determinant in Chronic Myelogenous Leukemia (2013)
  • Author(s): Takagi M, Sato M, Piao J, Miyamoto S, Isoda T, Kitagawa M, Honda H, Mizutani S
  • Journal Title: DNA Repair Volume: 12(7) Issue: 7 Pages: 500-507
  • DOI: 10.1016/j.dnarep.2013.04.022
  • Peer Reviewed
• [Journal Article] Artemis-dependent DNA double-strand break formation at stalled replication forks. (2013)
  • Author(s): Unno J, Takagi M, Piao J, Sugimoto M, Honda F, Maeda D, Masutani M, Kiyono T, Watanabe F, Morio T, Teraoka H, Mizutani S.
  • Journal Title: Cancer Sci. Volume: 104 Issue: 6 Pages: 703-10
  • DOI: 10.1111/cas.12144
  • Peer Reviewed
• [Journal Article] Ataxia telangiectasia mutated-dependent regulation of topoisomerase II alpha expression and sensitivity to topoisomerase II inhibitor (2013)
  • Author(s): Tamaichi H, Sato M, Porter AC, Shimizu T, Mizutani S, Takagi M
  • Journal Title: Cancer Sci Volume: 104(2) Issue: 2 Pages: 178-184
  • DOI: 10.1111/cas.12067
  • Peer Reviewed
• [Journal Article] Successful treatment of diffuse large B cell lymphoma in a patient with ataxia telangiectasia using rituximab (2013)
  • Author(s): Machida S, Tomizawa D, Tamaichi H, Okawa T, Endo A, Imai K, , Nagasawa M, Morio T, Mizutani S, Takagi M
  • Journal Title: J Pediatr Hematol Oncol Volume: 36 Issue: 6 Pages: 482-485
  • DOI: 10.1097/mph.0b013e3182804d59
  • Peer Reviewed
• [Journal Article] Process for immune defect and chromosomal translocation during early thymocyte development lacking ATM (2012)
  • Author(s): Isoda T, Takagi M, Piao J, Nakagama S,Sato M, Masuda K, Ikawa T, Azuma M, Morio T, Kawamoto H, Mizutani S
  • Journal Title: Blood Volume: 120(4) Issue: 4 Pages: 789-9
  • DOI: 10.1182/blood-2012-02-413195
  • Peer Reviewed
• [Journal Article] Functional characterization and targeted correction of ATM mutations identified in Japanese patients with ataxia-stelangiectasia (2011)
  • Author(s): Nakamura K, Du L, Tunuguntla R, Fike F, Cavalieri S, Morio T Mizutani S, Brusco A, Gatti RA
  • Journal Title: Hum Mutat Volume: vol.33 Issue: 1 Pages: 198-208
  • DOI: 10.1002/humu.21632
  • Peer Reviewed
• [Journal Article] Onset of quiescence following p53 mediated down-regulation of H2AX in normal cells (2011)
  • Author(s): Atsumi Y, Fujimori H, Fukuda H, Inase A, Shinohe K, Yoshioka Y, Shikanai M, Ichijima Y, Unno J, Mizutani S, Tsuchiya N, Hippo Y, Nakagama H, Masutani M, Teraoka H, Yoshioka K
  • Journal Title: PLoS One Volume: vol.6
  • Peer Reviewed
• [Presentation] ATM-dependent DNA damage-response pathway as a determinant in Chronic Myelogenous Leukemia (2013)
  • Author(s): Takagi M, Mizutani S
  • Organizer: ATW2013
  • Place of Presentation: Birmingham, UK
• [Presentation] E2A-HLF陽性急性リンパ性白血病に対するPARP阻害剤の有効性 (2013)
  • Author(s): 高木正稔, 益谷美都子, 水谷修紀
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜市、神奈川県
• [Presentation] Sensitivity to PARP inhibitor in acute lymphoblastic leukemia (2013)
  • Author(s): Masatoshi Takagi, Jinhua Piao, Takahiro Kamiya, Takeshi Inukai, Kanji Sugita, Kazuma Ohyashiki, Mitsuko Masutani, Shuki Mizutani
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: 札幌市、北海道
• [Presentation] ATM and haploinsufficiency acceleration of cancer development. International symposium 50th Anniversary of RIRBM (2012)
  • Author(s): Sato M, Takagi M, Piao J, Isoda1 T, Honda H, Yasuda A, Mizutani S
  • Organizer: Hiroshima University
  • Place of Presentation: Hiroshima
• [Presentation] Visualization of chromosomal translocation and early T-cell development failure in ATM deficiency (2012)
  • Author(s): Isoda1 T, Takagi M, Piao J, Sato M, Masuda K, Ikawa T, Azuma M, Morio T, Kawamoto H, Mizutani S
  • Organizer: 14th International workshop on Ataxia Telangiectasia
  • Place of Presentation: Delhi, India
• [Presentation] T-Cell Development Failure At β-Selection Checkpoint and TCRα/δ Locus Break Formation Associated with Chromosome 14 Translocation in Ataxia-Telangiectagia Mutated Deficient Mice (2012)
  • Author(s): Isoda T, Takagi M, Piao J, Nakagama S, Sato M, Masuda K, Ikawa T, Azuma M, Morio T, Kawamoto H, Mizutani S
  • Organizer: 53rd American society of hematology, annual meeting
  • Place of Presentation: San Diego
• [Presentation] 慢性骨髄性白血病 急性転化におけるDNA損傷応答機構の関与 (2012)
  • Author(s): 高木正稔
  • Organizer: 第54回日本小児血液・がん学会学術集会
  • Place of Presentation: 横浜
• [Presentation] ATM欠損T細胞分化のDN期におけるTリンパ球減少の原因と染色体転座の関係 (2012)
  • Author(s): 磯田健志
  • Organizer: 第115回日本小児科学会学術集会
  • Place of Presentation: 福岡