Establishment of scientific basis for iPS cell-rerived granulocyte transfusion strategy

• Project/Area Number: 26860474
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General internal medicine(including psychosomatic medicine)
• Research Institution: The University of Tokyo
• Principal Investigator: Yoshimi Akihide 東京大学, 医学部附属病院, 助教 (80609016)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: iPS細胞 / 顆粒球輸注 / 顆粒球輸血 / サイトカイン / がん / 化学療法 / 細胞株化 / 好中球 / 再生医療

Outline of Final Research Achievements

When the patients with cancer receive chemotherapies, white blood cells usually decrease and they have high risk for severe infection, which affect the treatment outcome. We need to have some novel strategies against this problem and granulocyte transfusion therapy is one of the excellent candidates to solve the issue. However, it is currently not widely used in the clinical setting because of physical and psychologic burdens and risk of donors. We developed a novel strategy to limitlessly obtain iPS cell-derived granulocytes by combining several gene transduction and cytokines for iPS cells.

Research Products

• [Journal Article] Recurrent CDC25C mutations drive malignant transformation in FPD/AML (2014)
  • Author(s): Yoshimi A, Toya T, Kawazu M, Ueno T, Tsukamoto A, Iizuka H, Nakagawa M, Nannya Y, Arai S, Harada H, Usuki K, Hayashi Y, Ito E, Kirito K, Nakajima H, Ichikawa M, Mano H, Kurokawa M
  • Journal Title: Nature communications Volume: 5 Issue: 1 Pages: 4770-4770
  • DOI: 10.1038/ncomms5770
  • Peer Reviewed / Open Access
• [Journal Article] Positive feedback between NF-κB and TNF-α promotes leukemia-initiating cell capacity. (2014)
  • Author(s): Kagoya Y, Yoshimi A, Kataoka K, Nakagawa M, Kumano K, Arai S, Kobayashi H, Saito T, Iwakura Y, Kurokawa M.
  • Journal Title: J Clin Invest. Volume: 124 Issue: 2 Pages: 528-542
  • DOI: 10.1172/jci68101
  • Peer Reviewed
• [Journal Article] JAK2V617F+ myeloproliferative neoplasm clones evoke paracrine DNA damage to adjacent normal cells through secretion of lipocalin-2. (2014)
  • Author(s): Kagoya Y, Yoshimi A, Tsuruta-Kishino T, Arai S, Satoh T, Akira S, Kurokawa M.
  • Journal Title: Blood Volume: 124 Issue: 19 Pages: 2996-3006
  • DOI: 10.1182/blood-2014-04-570572
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Inhibition of histone methyltransferase EZH2 depletes leukemia stem cell of mixed lineage leukemia fusion leukemia through upregulation of p16. (2014)
  • Author(s): Ueda K, Yoshimi A, Kagoya Y, Nishikawa S, Marquez VE, Nakagawa M, Kurokawa M.
  • Journal Title: Cancer Science Volume: （in press） Issue: 5 Pages: 0-0
  • DOI: 10.1111/cas.12386
  • Peer Reviewed
• [Journal Article] Development of hairy cell leukemia in familial platelet disorder with predisposition to acute myeloid leukemia. (2014)
  • Author(s): Toya T, Yoshimi A, Morioka T, Arai S, Ichikawa M, Usuki K, Kurokawa M
  • Journal Title: Platelets Volume: 25 Issue: 4 Pages: 300-302
  • DOI: 10.3109/09537104.2013.818636
  • Peer Reviewed
• [Journal Article] Evi1 defines leukemia-initiating capacity and tyrosine kinase inhibitor resistance in chronic myeloid leukemia. (2014)
  • Author(s): Sato T, Goyama S, Kataoka K, Nasu R, Tsuruta-Kishino T, Kagoya Y, Nukina A, Kumagai K, Kubota N, Nakagawa M, Arai S, Yoshimi A, Honda H, Kadowaki T, Kurokawa M.
  • Journal Title: Oncogene Volume: 33 Issue: 42 Pages: 5028-5038
  • DOI: 10.1038/onc.2014.108
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] EVI1 oncogene promotes KRAS pathway through suppression of microRNA-96 in pancreatic carcinogenesis. (2014)
  • Author(s): Tanaka M, Suzuki HI, Shibahara J, Kunita A, Isagawa T, Yoshimi A, Kurokawa M, Miyazono K, Aburatani H, Ishikawa S, Fukayama M.
  • Journal Title: Oncogene Volume: 33(19) Issue: 19 Pages: 2454-63
  • DOI: 10.1038/onc.2013.204
  • Peer Reviewed
• [Journal Article] Single-cell gene expression analysis reveals clonal architecture of blast-phase chronic myeloid leukaemia. (2013)
  • Author(s): Nukina A, Kagoya Y, Watanabe-Okochi N, Arai S, Ueda K, Yoshimi A, Nannya Y, and Kurokawa M.
  • Journal Title: Br J Haematol Volume: In Press Issue: 3 Pages: 580-91
  • DOI: 10.1111/bjh.12726
  • Peer Reviewed
• [Presentation] Modeling chronic myelomonocytic leukemia through patient-derived induced pluripotent stem cells (2014)
  • Author(s): Kazuki Taoka, Shunya Arai, Masataka Hosoi, Fumihiko Nakamura, Masashi Miyauchi, Sho Yamazaki, Akira Honda, Takashi Kobayashi, Keisuke Kataoka, Keiki Kumano, Akihide Yoshimi, Koji Eto, Hiromitsu Nakauchi, Tatsutoshi Nakahara, Mineo Kurokawa
  • Organizer: 第76回日本血液学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-31 – 2014-11-02
• [Presentation] Modeling chronic myelomonocytic leukemia through patient-derived induced pluripotent stem cells (2014)
  • Author(s): Kazuki Taoka, Shunya Arai, Masataka Hosoi, Fumihiko Nakamura, Masashi Miyauchi, Sho Yamazaki, Akira Honda, Takashi Kobayashi, Keisuke Kataoka, Keiki Kumano, Akihide Yoshimi, Koji Eto, Hiromitsu Nakauchi, Tatsutoshi Nakahara, Mineo Kurokawa
  • Organizer: 第73回日本癌学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Generation of iPSC from primary CML patient samples (2014)
  • Author(s): Akihide Yoshimi, Masashi Miyauchi, Tomohiko Sato, Keiki Kumano, Mineo Kurokawa
  • Organizer: 16th Annual John Goldman Conference on Chronic Myeloid Leukemia: Biology and Therapy
  • Place of Presentation: Philadelphia、USA
  • Year and Date: 2014-09-04 – 2014-09-07
  • Invited
• [Presentation] Recurrent CDC25C mutations drive malignant transformation in FPD/AML (2014)
  • Author(s): Akihide Yoshimi, Takashi Toya, Masahito Kawazu, Toshihide Ueno, Ayato Tsukamoto, Hiromitsu Iizuka, Masahiro Nakagawa, Yasuhito Nannya, Shunya Arai, Motoshi Ichikawa, Hironori Harada, Kensuke Usuki, Yasuhide Hayashi, Etsuro Ito, Keita Kirito, Hideaki Nakajima, Hiroyuki Mano, Mineo Kurokawa
  • Organizer: American Association for Cancer Research
  • Place of Presentation: San Diego、USA
  • Year and Date: 2014-04-05 – 2014-04-09
• [Remarks] Website_AkihideYoshimi
  • URL: https://sites.google.com/site/akihideyoshimi/website_akihideyoshimi