Elucidation of molecular mechanism of leukemogenesis with GATA1 and cohesin gene mutations

• Project/Area Number: 26461559
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Hirosaki University
• Principal Investigator: KANEZAKI RIKA 弘前大学, 医学研究科, 助教 (60722882)
• Co-Investigator(Renkei-kenkyūsha): ITO Etsuro 弘前大学, 大学院医学研究科, 教授 (20168339) ; TOKI Tsutomu 弘前大学, 大学院医学研究科, 講師 (50195731)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 白血病 / 転写因子 / コヒーシン

Outline of Final Research Achievements

It is known that children with Down syndrome are at about 10-20 times higher risk of leukemia than healthy children. About 10% of newborns with Down Syndrome develop a blood disease (TAM) in which immature megakaryocytes transiently proliferate, and about 20% of them progresses to megakaryocytic leukemia (ML-DS). The purpose of this study is to clarify the molecular mechanism for deveplopment of ML-DS.
In almost of all TAM and ML-DS, mutations of the megakaryocytic transcription factor GATA1 are detected. In this study, we revealed that GATA1 mutations affected the expression control of KIT gene which supports cell survival and proliferation. And, about the reserch of cohesin complex whose gene mutations are detected with high frequency in ML-DS, we are now investigating the effect on regulation of gene expression.

Research Products

• [Journal Article] ダウン症候群に伴うTAM発症の分子機構 (2015)
  • Author(s): 照井君典, 金崎里香, 土岐力, 伊藤悦朗
  • Journal Title: 日本産婦人科・新生児血液学会誌 Volume: 25 Pages: 49-54
• [Journal Article] 非ダウン症小児急性巨核芽球性白血病にみとめられた新規GATA1インフレーム変異 (2014)
  • Author(s): 王汝南, 金崎里香, 土岐力, 照井君典, 佐々木伸也, 工藤耕, 神尾卓哉, 佐藤知彦, 池田史圭, 荒木亮, 落合英俊, 伊藤悦朗
  • Journal Title: 弘前医学 Volume: 65 Pages: 227-237
  • NAID: 110009838312
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Dysregulation of the KIT gene expression by GATA1s in Down syndrome related myeloid disorders. (2016)
  • Author(s): 金崎里香, 土岐力, 照井君典, 佐々木伸也, 工藤耕, 神尾卓哉, 佐藤知彦, 池田史圭, 伊藤悦朗
  • Organizer: 第78回日本血液学会学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県）
  • Year and Date: 2016-10-13
• [Presentation] In-frame deletion of GATA1 in pediatric acute megakaryoblastic leukemia without Down syndrome. (2014)
  • Author(s): 金崎里香, 王汝南, 土岐力, 照井君典, 佐々木伸也, 工藤耕, 神尾卓哉, 池田史圭, 伊藤悦朗
  • Organizer: 第76回日本血液学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2014-10-31 – 2014-11-02
• [Remarks] 弘前大学「テニュアトラック普及・定着事業」
  • URL: http://www.med.hirosaki-u.ac.jp/tenure/researcher.html