Mechanism of bone marrow failure in aplastic anemia -Role of mesenchymal stem cell-

2008 Fiscal Year Final Research Report

• Project/Area Number: 19390283
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Nagoya University
• Principal Investigator: KOJIMA Seiji Nagoya University, 大学院・医学系研究科, 教授 (20313992)
• Co-Investigator(Kenkyū-buntansha): TAKAHASHI Yoshiyuki 名古屋大学, 医学部・附属病院, 助教 (40432273) ; YAGASAKI Hirosi 名古屋大学, 大学院・医学系研究科, 助教 (90378141)
• Project Period (FY): 2007 – 2008
• Keywords: 再生不良性貧血 / GATA-2 / 骨髄間葉系幹細胞 / PPARγ

Research Abstract

再生不良性貧血(再不貧)患者由来の骨髄間葉系幹細胞(MSC)における、T細胞機能抑制能の低下はみられない。一方再不貧では、骨髄微小環境におけるIFN-γが増加していることから、血液幹細胞(HSC)におけるGATA-2の発現が低下している。GATA-2の発現低下は、HSCの分化増殖を障害して造血能を低下させるとともに、脂肪細胞特異的遺伝子であるPPARγの発現を増強し、骨髄の脂肪化をもたらすものと考えられる。

Research Products

• [Journal Article] Immunosuppressive activity of mesenchymal stem cells is not decreased in children with aplastic anemia (2009)
  • Author(s): Xu Y, Takahashi Y, Yoshimi A, Tanaka M, Yagasaki H, Kojima S.
  • Journal Title: Int J Hematol. 89 Pages: 126-127
• [Journal Article] Japanese Childhood AML Cooperative Study Group. Prospective multicenter trial comparing repeated immunosuppressive therapy with stem-cell transplantation from an alternative donor as second-line treatment for children with severe and very severe aplastic anemia (2008)
  • Author(s): Kudo K, Kojima S, Tabuchi K, Yabe H, Tawa A, Imaizumi M, Hanada R, Hamamoto K, Kobayashi R, Morimoto A, Nakayama H, Tsuchida M, Horibe K, Kigasawa H, Tsukimoto I.
  • Journal Title: Blood 111 Pages: 1054-1059
• [Journal Article] Quantification of granulocyte-macrophage colony-stimulating factor hypersensitivity in juvenile myelomonocytic leukemia by 3H-thymidine assay (2008)
  • Author(s): Tanaka M, Takahashi Y, Xu Y, Yoshida N, Yoshimi A, Villalobos IB, Hama A, Nishio N, Hidaka H, Wang Y, Yagasaki H, Kojima S.
  • Journal Title: Leuk Res. 32 Pages: 1036-1042
• [Journal Article] Acute megakaryoblastic leukaemia (AMKL) in children: a comparison of AMKL with and without Down syndrome (2008)
  • Author(s): Hama A, Yagasaki H, Takahashi Y, Nishio N, Muramatsu H, Yoshida N, Tanaka M, Hidaka H, Watanabe N, Yoshimi A, Matsumoto K, Kudo K, Kato K, Horibe K, Kojima S.
  • Journal Title: Br J Haematol 140 Pages: 552-561
• [Journal Article] Japanese Childhood MDS Study Group. A conditioning regimen of busulfan, fludarabine, and melphalan for allogeneic stem cell transplantation in children with juvenile myelomonocytic leukemia (2008)
  • Author(s): Yabe M, Sako M, Yabe H, Osugi Y, Kurosawa H, Nara T, Tokuyama M, Adachi S, Kobayashi C, Yanagimachi M, Ohtsuka Y, Nakazawa Y, Ogawa C, Manabe A, Kojima S, Nakahata T
  • Journal Title: Pediatr Transplant 12 Pages: 862-867
• [Journal Article] Risk factors for early death in neonates with Down syndrome and transient leukaemia (2008)
  • Author(s): Muramatsu H, Kato K, Watanabe N, Matsumoto K, Nakamura T, Horikoshi Y, Mimaya J, Suzuki C, Hayakawa M, Kojima S.
  • Journal Title: Br J Haematol 142 Pages: 610-615
• [Journal Article] Clinical impact of HLA-DR15, a minor population of paroxysmal nocturnal haemoglobinuria -type cells, and an aplastic anaemia-associated autoantibody in children with acquired aplastic anaemia (2008)
  • Author(s): Yoshida N, Yagasaki H, Takahashi Y, Yamamoto T, Liang J, Wang Y, Tanaka M, Hama A, Nishio N, Kobayashi R, Hotta N, Asami K, Kikuta A, Fukushima T, Hirano N, Kojima S.
  • Journal Title: Br J Haematol Epub ahead of print
• [Journal Article] Japanese epidemiological survey with consensus statement on Japanese guidelines for treatment of iron overload in bone marrow failure syndromes (2008)
  • Author(s): Suzuki T, Tomonaga M, Miyazaki Y, Nakao S, Ohyashiki K, Matsumura I, Kohogo Y, Niitsu Y, Kojima S, Ozawa K.
  • Journal Title: Int J Hematol 88 Pages: 30-35
• [Journal Article] Japan Cord Blood Bank Network. Unrelated cord blood transplantation for severe aplastic anemia. Biol Blood Marrow Transplant (2008)
  • Author(s): Yoshimi A, Kojima S, Tanigushi S, Hara J, Matsui T, Takahashi Y, Azuma H, Kato K, Nagamura-Inoue T, Kai S, Kato S
  • Journal Title: Biol Blood Marrow Transplant 14 Pages: 1057-1063
• [Journal Article] Congenital erythroid and myeloid hypoplasia terminating myelodysplastic syndrome (2008)
  • Author(s): Nishio N, Yagasaki Y, Takahashi Y, Muramatsu H, Hama A, Zu Y, Villalobos IB, Kojima S.
  • Journal Title: J Pediatr Hematol Oncol 30 Pages: 692-695
• [Journal Article] Outcome of bone marrow transplantation from HLA-identical sibling donor in children with hematological malignancies using methotrexate alone as prophylaxis for graft-versus-host disease (2008)
  • Author(s): Watanabe N, Matsumoto K, Yoshimi A, Horibe K, Matsuyama T, Kojima S, Kato K.
  • Journal Title: Int J Hematol 88 Pages: 575-582
• [Journal Article] Correlation of clinical features with the mutational status of GM-CSF signaling pathway-related genes in juvenile myelomonocytic leukemia (2008)
  • Author(s): Yoshida N, Yagasaki H, Xu Y, Matsuda K, Yoshimi A, Takahashi Y, Hama A, Nishio N, Muramatsu H, Watanabe N, Matsumoto K, Kato K, Ueyama J, Inada H, Goto H, Yabe M, Kudo K, Miyama J, Kikushi A, Manabe A, Koike K, Kojima S.
  • Journal Title: Pediatr Res. [Epub ahead of print]
• [Journal Article] Engraftment syndrome following allogeneic hematopoietic stem cell transplantation in children (2008)
  • Author(s): Nishio N, Yagasaki H, Takahashi Y, Hama A, Muramatsu H, Tanaka M, Yoshida N, Yoshimi A, Kudo K, Ito M, Kojima S.
  • Journal Title: Pediatr Transplant [Epub ahead of print]
• [Journal Article] Increased midkine gene expression in childhood B-precursor acute lymphoblastic leukemia (2007)
  • Author(s): Hidaka M, Yagasaki H, Takahashi Y, Hama A, Nishio N, Tanaka M, Yoshida N, Villalobos IB, Wang Y, Xu Y, Horibe K, Dhen S, Kadomatsu K, Kojima S.
  • Journal Title: Leuk Res. 83 Pages: 535-540
• [Journal Article] Spontaneous improvement of hematologic abnormalities in patients having juvenile myelomonocytic leukemia with specific RAS mutations (2007)
  • Author(s): Matsuda K, Shimada A, Yoshida N, Ogawa A ,Watanabe A, Yajima S, Iizuka S, Koike K, Yanai F, Kawasaki K, Yanagimachi M, Kikushi A, Ohtsuka Y, Hidaka E, Yamaguchi K, Tanaka M, Yanagisawa R, Nakazawa Y, Shiohara M, Manabe A, Kojima S.
  • Journal Title: Blood 109 Pages: 544
• [Journal Article] Feasibility and results of bone marrow transplantation from an HLA-mismatched unrelated donor for children and young adults with acquired severe aplastic anemia (2007)
  • Author(s): Yagasaki H, Takahashi Y, Kudo K, Ohashi H, Hama A, Yamamoto T, Tanaka M, Yoshida N, Hidaka H, Nishio N, Kojima S.
  • Journal Title: Int J Haematol 85 Pages: 437-442
• [Journal Article] Mutation of SBDS and SH2D1A is not associated with aplastic anemia in Japanese children (2007)
  • Author(s): Wang Y, Yagasaki H, Hama A, Nishio N, Takahashi Y, Kojima S.
  • Journal Title: Haematologica 92 Pages: 1573
• [Journal Article] Japanese Childhood AML Cooperative Study Group. Prospective study of a pirarubicin, intermediate-dose cytarabine, and etoposide regimen in children with Down syndrome and acute myeloid leukemia: the Japanese Childhood AML Cooperative Study Group (2007)
  • Author(s): Kudo K, Kojima S, Tabuchi K, Yabe H, Tawa A, Imaizumi M, Hanada R, Hamamoto K, Kobayashi R, Morimoto A, Nakayama H, Tsuchida M, Horibe K, Kigasawa H, Tsukimoto I
  • Journal Title: J Clin Oncol 25 Pages: 5442-5447
• [Journal Article] Japan Childhood Aplastic Anemia Study Group. Antithymocyte globulin and cyclosporine for treatment of 44 children with hepatitis associated aplastic anemia (2007)
  • Author(s): Osugi Y, Yagasaki H, Sako M, Kosaka Y, Taga T, Ito T, Yamamoto M, Ohara A, Sato T, Mimaya J, Tsukimoto I, Kojima S
  • Journal Title: Haematologica 92 Pages: 1687-1690
• [Presentation] Bone Marrow Transplantation for Children with chronic myeloid leukemia (CML): A Report from the Japan Marrow Donor Program (JMDP) (2008)
  • Author(s): Muramatsu H, Kojima S, et. al.
  • Organizer: 50th Annual Meeting of the American Society of Hematology
  • Place of Presentation: Atlanta USA
  • Year and Date: 20081208-11
• [Presentation] Predicting response to immunosuppressive therapy in childhood aplastic anemia (2008)
  • Author(s): Yoshida N, Kojima S, et. al.
  • Organizer: 50th Annual Meeting of the American Society of Hematology
  • Place of Presentation: Atlanta USA
  • Year and Date: 20081208-11
• [Presentation] Gene alterations and expression of hematopoietic transcription factors in pediatric acute megakaryobblastic leukemia (AMKL): A Comparison of Down Syndrome (DS)-associated AMKL with Non-DS-AMKL (2008)
  • Author(s): Hama A, Kojima S, et. al.
  • Organizer: 50th Annual Meeting of the American Society of Hematology
  • Place of Presentation: Atlanta USA
  • Year and Date: 20081208-11
• [Presentation] Myelodysplastic Syndrome (MDS) and myeloproliferative disease (MPD) in children: A Prospective registrarion of 222 Cases (2008)
  • Author(s): Manabe A, Kojima S, et. al.
  • Organizer: 50th Annual Meeting of the American Society of Hematology
  • Place of Presentation: Atlanta USA
  • Year and Date: 20081208-11
• [Presentation] Mismatching at HLA-DPB1 is Not associated with survival in patients with acquired aplastic anemia who receive unrelated bone marrow transplantation (2008)
  • Author(s): Yagasaki H, Kojima S, et. al.
  • Organizer: 50th Annual Meeting of the American Society of Hematology
  • Place of Presentation: Atlanta USA
  • Year and Date: 20081208-11
• [Presentation] Relapse of children with aplastic anemia after immunosuppressive therapy (2008)
  • Author(s): Kamati Y, Kojima S, et. al.
  • Organizer: 50th Annual Meeting of the American Society of Hematology
  • Place of Presentation: Atlanta USA
  • Year and Date: 20081208-11
• [Presentation] Improved outcome of unrelated bone marrow transplantation for severe aplastic anemia (2008)
  • Author(s): Yagasaki H, Kojima S, et. al.
  • Organizer: 49th Annual Meeting of the American Society of Hematology
  • Place of Presentation: Atlanta USA
  • Year and Date: 20081208-11
• [Presentation] Should hematopoietic stem cell transplantation in first complete remission be restricted to high-risk patients in childhood acute myeloid leukemia (2008)
  • Author(s): Muramatsu H, Kojima S, et. al.
  • Organizer: 49th Annual Meeting of the American Society of Hematology
  • Place of Presentation: Atlanta USA
  • Year and Date: 20081208-11
• [Presentation] JAK3, JAK2 and GATA1 mutations in childhood acute megakaryoblastic leukemia with and without down syndrom (2008)
  • Author(s): Hama A, Kojima S, et. al.
  • Organizer: 49th Annual Meeting of the American Society of Hematology
  • Place of Presentation: Atlanta USA
  • Year and Date: 20081208-11
• [Presentation] Decreased incidence of clonal evolution to myelodysplastic syndrome/ acute myeloid leukemia with monosomy7 in children with aplastic anemia following reduced use of G-CSF (2008)
  • Author(s): Takahashi Y, Kojima S, et. al.
  • Organizer: 49th Annual Meeting of the American Society of Hematology
  • Place of Presentation: Atlanta USA
  • Year and Date: 20081208-11
• [Presentation] Natural History of Transfusion-independent non-Severe Aplastic Anemia in Children (2008)
  • Author(s): Nishio N, Kojima S, et. al.
  • Organizer: 49th Annual Meeting of the American Society of Hematology
  • Place of Presentation: Atlanta USA
  • Year and Date: 20081208-11
• [Presentation] Correlation of clinical features with the mutational status of GM-CSF signaling Pathway-related genes in children with juvenile myelomonocytic leukemia (2008)
  • Author(s): Yoshida N, Kojima S, et. al.
  • Organizer: 49th Annual Meeting of the American Society of Hematology
  • Place of Presentation: Atlanta USA
  • Year and Date: 20081208-11
• [Presentation] Therapeutic strategies and clinical results in JMML-Update on Japanese trial (2008)
  • Author(s): Kojima S
  • Organizer: 2nd JMMLsymposium
  • Place of Presentation: Atlanta USA
  • Year and Date: 20081206-07
• [Book] 小児科第3版 (2008)
  • Author(s): 小島勢二, 他
  • Total Pages: 1277-1281
  • Publisher: 医学書院
• [Book] 小児科診療ガイドライン-最新の診療指針- (2007)
  • Author(s): 小島勢二, 他
  • Total Pages: 230-233
  • Publisher: 総合医学社