Characterizing the large chromosomal deletion in 7q- myelodysplastic syndrome using human iPS cells and the genome editing system

• Project/Area Number: 16K19575
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Hiroshima University
• Principal Investigator: Nagamachi Akiko 広島大学, 原爆放射線医科学研究所, 助教 (20585153)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 骨髄異形成症候群 / 遺伝子 / 白血病

Outline of Final Research Achievements

Monosomy 7 and interstitial deletion of 7q is a well-recognized nonrandom chromosomal abnormality frequently found among patients with myelodysplastic syndromes and myeloid leukemias. To understand the effects of lacking large deletion on chromosome 7 in hematopoietic cell differentiation, I constructed in vitro model systems using human induced pluripotent stem (iPS) cells and the genome editing system. I suceeded in generating iPS cells carrying 7q that lacks various large regions using the CRISPR/Cas9 genome editing system, and plan to induce these cells to differentiate into multiple hematopoietic cells via the method of the formation of embryoid bodies to examine the hematopoietic function.

Research Products

• [Journal Article] A paralogous pair of mammalian host restriction factors form a critical host barrier against poxvirus infection. (2018)
  • Author(s): Meng X, Zhang F, Yan B, Si C, Honda H, Nagamachi A, Sun LZ, Xiang Y.
  • Journal Title: PLoS Pathog. Volume: 14 Issue: 2 Pages: e1006884-e1006884
  • DOI: 10.1371/journal.ppat.1006884
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Acquired expression of CblQ367P in mice induces dysplastic myelopoiesis mimicking chronic myelomonocytic leukemia (2017)
  • Author(s): Nakata Y, Ueda T, Nagamachi A, Yamasaki N, Ikeda KI, Sera Y, Takubo K, Kanai A, Oda H, Sanada M, Ogawa S, Tsuji K, Ebihara Y, Wolff L, Honda ZI, Suda T, Inaba T, Honda H.
  • Journal Title: Blood Volume: 129 Issue: 15 Pages: 2148-2160
  • DOI: 10.1182/blood-2016-06-724658
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Propagation of tri-methylated H3K27 regulated by EED is required for embryogenesis, hematopoietic maintenance, and tumor suppression. (2016)
  • Author(s): Ueda T, Nakata Y, Nagamachi A, Yamasaki N, Kanai A, Matsui H, Honda ZI, Oda H, Wolff L, Inaba T, Honda H.
  • Journal Title: PNAS Volume: 113(37) Issue: 37 Pages: 10370-10375
  • DOI: 10.1073/pnas.1600070113
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Maintenance of the functional integrity of mouse hematopoiesis by EED and promotion of leukemogenesis by EED haploinsufficiency (2016)
  • Author(s): Ikeda K-I, Ueda T, Yamasaki N, Nakata Y, Sera Y, Nagamachi A, Miyama T, Kobayashi H, TakuboK, Kanai A, Oda H, Wolff l, Honda Z-1, Ichinohe T, Matsubara A, Suda T, Inaba T, Honda H
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 29454-29454
  • DOI: 10.1038/srep29454
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Biological implication of somatic DDX41 p.R525H mutation in acute myeloid leukemia. (2016)
  • Author(s): Kadono M, Kanai A, Nagamachi A, Shinriki S, Kawata J, Iwato K, Kyo T, Oshima K, Yokoyama A, Kawamura T, Nagase R, Inoue D, Kitamura T, Inaba T, Ichinohe T, Matsui H.
  • Journal Title: Exp. Hematol. Volume: 44(8) Issue: 8 Pages: 745-754
  • DOI: 10.1016/j.exphem.2016.04.017
  • Peer Reviewed / Open Access
• [Journal Article] Identification of cooperative genes for E2A-PBX1 to develop acute lymphoblastic leukemia. (2016)
  • Author(s): Sera Y, Yamasaki N, Oda H, Nagamachi A, Wolff L, Inukai T, Inaba T, Honda H.
  • Journal Title: Cancer Sci Volume: 107 Issue: 7 Pages: 890-898
  • DOI: 10.1111/cas.12945
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] The role of Samd9 and Samd9L in the early endocytotic pathway (2017)
  • Author(s): Akiko Nagamachi, Hirotaka Matsui, Akinori Kanai, Hiroaki Honda and Toshiya Inaba
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] The role of Samd9 and Samd9L in the early endocytotic pathway (2017)
  • Author(s): Akiko Nagamachi, Hirotaka Matsui, Akinori Kanai, Hiroaki Honda and Toshiya Inaba
  • Organizer: 第79回日本血液学会学術集会
• [Presentation] Low Miki expression in myelodysplastic syndromes enhance the formation of polynuclear cell (2016)
  • Author(s): 長町安希子, 尾崎祐子、松井啓隆, 金井昭教, 稲葉俊哉
  • Organizer: 第78回日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-13
• [Presentation] eEF1A2 is a target gene of DNA demethylating agents for improving anemia of MDS (2016)
  • Author(s): 長町安希子
  • Organizer: 第75回日本癌学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-06