Investigation of pathogenesis of leukemia in Down syndrome patients using human ES and iPS cells

• Project/Area Number: 15K15402
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Embryonic/Neonatal medicine
• Research Institution: The University of Tokyo
• Principal Investigator: MOCHIZUKI SHINJI 東京大学, 医科学研究所, 特任助教 (90349473)
• Co-Investigator(Kenkyū-buntansha): OTSU Makoto 東京大学, 医科学研究所, 准教授 (30361330) ; EBIHARA Yasuhiro 東京大学, 医科学研究所, 特任准教授 (40302608)
• Project Period (FY): 2015-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
• Keywords: 遺伝・先天異常学 / iPS細胞 / 遺伝・先天性異常学

Outline of Final Research Achievements

To clarify the mechanism causing hematological disorders and leukemia in DS patients, we employed induced pluripotent stem (iPS) cells derived from patients with DS and control iPS cells from healthy donor reprogrammed by the defined 3 or 4 factors (OCT3/4, KLF4, SOX2, and with or without c-MYC). We generated blood cells from DS and control iPS cells co-cultured with murine aorta-gonad-mesonephros-derivedstromal cell line. The harvested cells were analyzed for the presence of hematopoietic markers and the potentials of hematopoietic colony formation. Our results indicated that DS iPS cells could differentiate into identify the responsible genes for the acceleration of hematopoiesis in DS iPS cells, we carried out micro array analysis of hematopoietic cells derived from DS or control iPS cells. We then detected the high expression of 18 genes on chromosome 21 including RUNX1.

Research Products

• [Journal Article] Residual disease detected by multidimensional flow cytometry shows prognostic significance in childhood acute myeloid leukemia with intermediate cytogenetics and negative FLT3-ITD: a report from the Tokyo Children's Cancer Study Group. (2016)
  • Author(s): Keino D, Kinoshita A, Tomizawa D, Takahashi H, Ida K, Kurosawa H, Koike K, Ota S, Iwasaki N, Fujimura J, Yuza Y, Kiyotani C, Yamamoto S, Osumi T, Ueda T, Mochizuki S, Isoyama K, Hanada R, Tawa A, Manabe A, Toguchi Y, Ohara A.
  • Journal Title: Int J Hematol. Volume: 103 Pages: 416-22
  • Peer Reviewed
• [Journal Article] Third allogeneic stem cell transplantation (SCT) using unrelated cord blood for relapsed acute leukemia after second allogeneic SCT. (2015)
  • Author(s): Konuma T, Kato S, Ooi J, Ebihara Y, Mochizuki S, Oiwa-Monna M, Tojo A, Takahashi S.
  • Journal Title: International journal of hematology. Volume: 101(4) Issue: 4 Pages: 392-7
  • DOI: 10.1007/s12185-015-1755-7
  • Peer Reviewed / Open Access
• [Journal Article] Curative haploidentical BMT in a murine model of X-linked chronic granulomatous disease. (2015)
  • Author(s): Takeuchi Y, Takeuchi E, Ishida T, Onodera M, Nakauchi H, Ohtsu M.
  • Journal Title: Int J Hematol Volume: 102(1) Issue: 1 Pages: 111-120
  • DOI: 10.1007/s12185-015-1799-8
  • Peer Reviewed / Open Access
• [Journal Article] <b>Hyaline cartilage formation and tumorigenesis of implanted tissues derived from human induced pluripotent stem </b><b>cells </b> (2015)
  • Author(s): Saito T, Yano F, Mori D, Kawata M, Hoshi K, Takato T, Masaki H, Otsu M, Eto K, Nakauchi H, Chung UI, Tanaka S
  • Journal Title: Biomedical Research Volume: 36 Issue: 3 Pages: 179-186
  • DOI: 10.2220/biomedres.36.179
  • NAID: 130005083858
  • ISSN: 0388-6107, 1880-313X
  • Peer Reviewed / Open Access
• [Book] Annual Review 血液 2016 (2016)
  • Author(s): 編集 ／ 高久史麿他、著者／ 大津真他
  • Total Pages: 236
  • Publisher: 中外医学社