Development of therapeutic approach targeting DNA damage check point

2013 Fiscal Year Final Research Report

• 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
• Keywords: 小児血液学 / DNA損傷応答

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) 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, PiaoJ, SugimotoM, Honda F, Maeda D, Masutani M, Kiyono T, Watanabe F, Morio T Teraoka H, Mizutani S
  • Journal Title: Cancer Sci Volume: 104(6) Pages: 703-710
  • 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) Pages: 178-184
  • DOI: 10.1111/cas.12067
  • 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) Pages: 789-799
  • DOI: 10.1182/blood-2012-02-413195
  • 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
  • Year and Date: 20130728-31
• [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
  • Year and Date: 20121210-13
• [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
  • Year and Date: 20120220-21
• [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
  • Year and Date: 20120207-11