Analysis of occurrence of leukemia from congenital bone marrow failure syndrome and establishment of its treatment using human iPS cells

• Project/Area Number: 26670511
• 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: EBIHARA Yasuhiro 東京大学, 医科学研究所, 特任准教授 (40302608)
• Co-Investigator(Kenkyū-buntansha): OTSU Makoto 東京大学, 医科学研究所, 准教授 (30361330) ; MOCHIZUKI Shinji 東京大学, 医科学研究所, 特任助教 (90349473)
• Project Period (FY): 2014-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
• Keywords: 先天異常学

Outline of Final Research Achievements

Severe congenital neutropenia (SCN) and cyclic neutropenia (CyN) are belonged to congenital bone marrow failure syndrome (CBMFS). Acute myelogenous leukemia (AML) was sometimes developed in the patients with some CBMFS including SCN. No AML occurred in the patients with CyN. To investigate the mechanism of AML occurrence, we established iPS cells from the patients (both had mutation in ELANE gene region) with SCN (SCN-iPS cells) or CyN (CyN-iPS cells), respectively. Myeloid cells derived from CyN-iPS cells revealed that the capability to differentiate into hematopoietic cells including neutrophils was almost similar to control iPS cells. SCN-iPS cells showed decreased capability into neutrophils, reflecting the disease status of SCN patients. To compare the mechanism of hematopoietic differentiation from SCN- and CyN-iPS cells was expected to be useful to analyze the mechanism of the onset of AML and treatment of these AML.

Research Products

• [Journal Article] In vitro expansion of CD34(+)CD38(-) cells under stimulation with hematopoietic growth factors on AGM-S3 cells in juvenile myelomonocytic leukemia. (2015)
  • Author(s): Sakashita K, Kato I, Daifu T, Saida S, Hiramatsu H, Nishinaka Y, Ebihara Y, Ma F, Matsuda K, Saito S, Hirabayashi K, Kurata T, Uyen Lt, Nakazawa Y, Tsuji K, Heike T, Nakahata T, Koike K.
  • Journal Title: Leukemia. Volume: 29(3) Issue: 3 Pages: 606-14
  • DOI: 10.1038/leu.2014.239
  • NAID: 120007110642
  • Peer Reviewed / Open Access
• [Journal Article] Allogeneic stem cell transplantation for patients with acute myeloid leukemia developing from severe congenital neutropenia. (2014)
  • Author(s): Ebihara Y, Ishikawa K, Mochizuki S, Tanaka R, Manabe A, Iseki T, Maekawa T, Tsuji K.
  • Journal Title: Br J Haematol. Volume: 164 Issue: 3 Pages: 451-464
  • DOI: 10.1111/bjh.12638
  • Peer Reviewed / Open Access
• [Journal Article] Impact of sex incompatibility on the outcome of single-unit cord blood transplantation for adult patients with hematological malignancies. (2014)
  • Author(s): Konuma T, Tojo A, et al.
  • Journal Title: Bone Marrow Transplant. Volume: 49 Issue: 5 Pages: 634-9
  • DOI: 10.1038/bmt.2014.10
  • Peer Reviewed / Open Access
• [Journal Article] Effect of ABO Blood Group Incompatibility on the Outcome of Single-Unit Cord Blood Transplantation after Myeloablative Conditioning (2014)
  • Author(s): Konuma T, Tojo A, et al.
  • Journal Title: Biol Blood Marrow Transplant. Volume: 20 Issue: 4 Pages: 577-581
  • DOI: 10.1016/j.bbmt.2013.12.563
  • Peer Reviewed / Open Access
• [Journal Article] Acquired deficiency of A20 results in rapid apoptosis, systemic inflammation, and abnormal hematopoietic stem cell function. (2014)
  • Author(s): Nagamachi A, Nakata Y, Ueda T, Yamasaki N, Ebihara Y, Tsuji K, Honda Zi, Takubo K, Suda T, Oda H, Inaba T, Honda H
  • Journal Title: PLos One Volume: 9 Issue: 1 Pages: 1-10
  • DOI: 10.1371/journal.pone.0087425
  • Peer Reviewed / Open Access
• [Journal Article] Impaired hematopoietic differentiation of RUNX1-mutated induced pluripotent stem cells derived from FPD/AML patients (2014)
  • Author(s): Sakurai M, Kunimoto H, Watanabe N, Fukuchi Y, Yuasa S, Yamazaki S, Nishimura T, Sadahira K, Fukuda K, Okano H, Nakauchi H, Morita Y, Matsumura I, Kudo K, Ito E, Ebihara Y, Tsuji K, Harada Y, Harada H, Okamoto S, Nakajima H
  • Journal Title: Leukemia Volume: 28 Issue: 12 Pages: 2344-54
  • DOI: 10.1038/leu.2014.136
  • Peer Reviewed / Open Access
• [Presentation] RCCに対して同種臍帯血移植を施行した2例 (2014)
  • Author(s): 海老原 康博, 望月 慎史, 大津 真, 辻 浩一郎
  • Organizer: 日本小児血液・がん学会
  • Place of Presentation: 岡山コンベンションセンター（岡山県岡山市）
  • Year and Date: 2014-11-28 – 2014-11-30
• [Book] 遺伝子医学MOOK(1349-2527)27号 (2015)
  • Author(s): 海老原 康博
  • Total Pages: 8
  • Publisher: メディカル ドゥ