A role for ATOX1 in 5q- syndrome

2013 Fiscal Year Final Research Report

• Project/Area Number: 24659467
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Hematology
• Research Institution: Keio University
• Principal Investigator: NAKAJIMA Hideaki 慶應義塾大学, 医学部, 准教授 (30217723)
• Co-Investigator(Kenkyū-buntansha): OKAMOTO Shinichiro 慶應義塾大学, 医学部, 教授 (50160718)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 5q-症候群 / 骨髄異形成症候群 / ATOX1 / 造血幹細胞

Research Abstract

5q- syndrome is a subtype of myelodysplastic syndrome characterized by a deletion of chromosome 5q33. To elucidate molecular pathogenesis of 5q- syndrome, we focused on ATOX1, a cupper chaperone located in the common deleted region of 5q33. Frequencies of hematopoietic stem cells (HSCs), multipotent hematopoietic progenitors, and lineage-committed progenitors in the bone marrow were normal in ATOX1-/- mice, and ATOX1-/- HSCs maintained normal self-renewal and long-term repopulating capacities. These results suggest that ATOX1 is not essential for HSC function and hematopoietic differentiation, and that ATOX1 has little, if any, roles in 5q- syndrome.

Research Products

• [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: Apr 15
  • DOI: 10.1038/leu.2014.136
  • Peer Reviewed
• [Journal Article] Tet2-mutated myeloid progenitors possess aberrant in vitro self-renewal capacity (2014)
  • Author(s): Kunimoto H, Fukuchi Y, Sakurai M, Takubo K, Okamoto S, Nakajima H.
  • Journal Title: Blood Volume: 123 Pages: 2897-9
  • Peer Reviewed
• [Journal Article] Plzf drives MLL-fusion-mediated leukemogenesis specifically in long term hematopoietic stem cells (2013)
  • Author(s): Ono R, Masuya M, Nakajima H, Enomoto Y, Miyata E, Nakamura A, Ishii S, Suzuki K, Shibata-Minoshima F, Katayama N, Kitamura T, Nosaka T.
  • Journal Title: Blood Volume: 122 Pages: 1271-83
  • Peer Reviewed
• [Journal Article] Tet2 disruption leads to enhanced self-renewal and altered differentiation of fetal liver hematopoietic stem cells (2012)
  • Author(s): Kunimoto H, Fukuchi Y, Sakurai M, Sadahira K, Ikeda Y, Okamoto S, Nakajima H.
  • Journal Title: Scientific Reports Volume: 2 Pages: 273
  • Peer Reviewed
• [Journal Article] Direct reprogramming of terminally differentiated B cells into erythroid lineage (2012)
  • Author(s): Sadahira K, Fukuchi Y, Kunimono H, Sakurai M, Ikeda Y, Okamoto S, Nakajima H.
  • Journal Title: FEBS Letters Volume: 586 Pages: 3645-52
  • Peer Reviewed
• [Journal Article] Robo4 plays a role in bone marrow homing and mobilization, but is not essential in the long-term repopulating capacity of hematopoietic stem cells (2012)
  • Author(s): Goto-Koshino Y, Fukuchi Y, Shibata F, Abe D, Kuroda K, Okamoto S, Kitamura T, Nakajima H.
  • Journal Title: PLOS ONE Volume: 7 Pages: e50849
  • Peer Reviewed
• [Presentation] The Genetic Landscape of FPD/AML Revealed CDC25C Mutation as a Driver that Promotes Malignant Transformation (2013)
  • Author(s): Akihide Yoshimi, Takashi Toya, Masahiro Nakagawa, Masahito Kawazu, Yasuhito Nannya, Motoshi Ichikawa, Shunya Arai, Hironori Harada, Kensuke Usuki, Yasuhide Hayashi, Etsuro Ito, Keita Kirito, Hideaki Nakajima, Hiroyuki Mano, Mineo Kurokawa
  • Organizer: 55th Annual Meeting of American Society of Hematology, Simultaneous Session
  • Place of Presentation: 米国、ニューオーリンズ
  • Year and Date: 2013-12-09
• [Presentation] Chemo-Immunotherapy With Hyper-CVAD/MA and Rituximab For B-Cell Lymphomas Leads To Prolonged Immune Suppression Compared To Conventional Treatment With R-CHOP (2013)
  • Author(s): Eri Matsuki, Taku Kikuchi, Norisato Hashimoto, Shunsuke Souma, Sumiko Kohashi, Takaaki Toyama, Masatoshi Sakurai, Daiki Karigane, Daichi Abe, Takayuki Shimizu, Kenji Yokoyama, Hideaki Nakajima, Shinichiro Okamoto
  • Organizer: 55th Annual Meeting of American Society of Hematology, Simultaneous Session
  • Place of Presentation: 米国、ニューオーリンズ
  • Year and Date: 2013-12-09
• [Presentation] Impaired emergence of hematopoietic progenitors and defective megakaryocyte differentiation from FPD/AML-derived induced pluripotent stem cells (2013)
  • Author(s): Masatoshi Sakurai, Hiroyoshi Kunimoto, Naohide Watanabe, Yumi Fukuchi, Shinsuke Yuasa, Keiichi Fukuda, Satoshi Yamazaki, Hiromitsu Nakauchi, Yasuhiro Ebihara, Koichiro Tsuji, Etsuro Ito, Yuka Harada, Hironori Harada, Shinichiro Okamoto, Hideaki Nakajima
  • Organizer: EMBO Workshop-RUNX transcription factors in development and disease
  • Place of Presentation: ドイツ、Wilsede
  • Year and Date: 2013-06-17
• [Presentation] Impaired hematopoietic differentiation of iPSCs derived from patients with FPD/AML (2012)
  • Author(s): Masatoshi Sakurai, Hiroyoshi Kunimoto, Naohide Watanabe, Yumi Fukuchi, Ken Sadahira, Shinsuke Yuasa, Keiichi Fukuda, Satoshi Yamazaki, Hiromitsu Nakauchi, Yasuhiro Ebihara, Koichiro Tsuji, Etsuro Ito, Yuka Harada, Hironori Harada, Shinichiro Okamoto, Hideaki Nakajima
  • Organizer: 54th Annual Meeting of American Society of Hematology, Simultaneous Session
  • Place of Presentation: 米国、アトランタ
  • Year and Date: 2012-12-10
• [Presentation] Tet2 Uniquely Regulates Self-Renewal and Long Term Repopulating Capacity of Fetal Liver and Bone Marrow Hematopoietic Stem Cells (2012)
  • Author(s): Hiroyoshi Kunimoto, Yumi Fukuchi, Masatoshi Sakurai, Daichi Abe, Ken Sadahira, Yasuo Ikeda, Shinichiro Okamoto, Hideaki Nakajima
  • Organizer: 54th Annual Meeting of American Society of Hematology, Simultaneous Session
  • Place of Presentation: 米国、アトランタ
  • Year and Date: 2012-12-10
• [Presentation] Reprogramming of mature B cells into erythroid lineage (2012)
  • Author(s): Ken Sadahira, Yumi Fukuchi, Hiroyoshi Kunimoto, Masatoshi Sakurai, Shinichiro Okamoto, Hideaki Nakajima
  • Organizer: 10^<th> Annual Meeting of International Society of Stem Cell Research
  • Place of Presentation: 横浜
  • Year and Date: 2012-06-15
• [Presentation] Disruption of Tet2 leads to enhanced self-renewal and competitive repopulating capacity of fetal liver hematopoietic stem cells (2012)
  • Author(s): Hiroyoshi Kunimoto, Yumi Fukuchi , Masatoshi Sakurai, Ken Sadahira, Yasuo Ikeda, Shinichiro Okamoto, Hideaki Nakajima
  • Organizer: 10^<th> Annual Meeting of International Society of Stem Cell Research
  • Place of Presentation: 横浜
  • Year and Date: 2012-06-15