小児再生不良性貧血の造血障害メカニズム-骨髄間葉系細胞の関与-

• 研究課題/領域番号: 19390283
• 研究種目: 基盤研究(B)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 小児科学
• 研究機関: 名古屋大学
• 研究代表者: 小島 勢二 名古屋大学, 大学院・医学系研究科, 教授 (20313992)
• 研究分担者: 高橋 義行 名古屋大学, 医学部・附属病院, 助教 (40432273) ; 谷ヶ崎 博 (谷ケ崎 博) 名古屋大学, 大学院・医学系研究科, 助教 (90378141)
• 研究期間 (年度): 2007 – 2008
• 研究課題ステータス: 完了 (2008年度)
• 配分額: 8,320千円 (直接経費: 6,400千円、間接経費: 1,920千円); 2008年度: 3,250千円 (直接経費: 2,500千円、間接経費: 750千円); 2007年度: 5,070千円 (直接経費: 3,900千円、間接経費: 1,170千円)
• キーワード: 再生不良性貧血 / GATA-2 / 骨髄間葉系幹細胞 / PPARγ / 脂肪特異的転写因子

研究概要

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。

研究成果

• [雑誌論文] Immunosuppressive activity of mesenchymal stem cells is not decreased in children with aplastic anemia (2009)
  • 著者名/発表者名: Xu Y, Takahashi Y, Yoshimi A, Tanaka M, Yagasaki H, Kojima S.
  • 雑誌名: Int J Hematol. 89 ページ: 126-127
  • NAID: 10025159958
• [雑誌論文] 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)
  • 著者名/発表者名: 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.
  • 雑誌名: Blood 111 ページ: 1054-1059
• [雑誌論文] Quantification of granulocyte-macrophage colony-stimulating factor hypersensitivity in juvenile myelomonocytic leukemia by 3H-thymidine assay (2008)
  • 著者名/発表者名: Tanaka M, Takahashi Y, Xu Y, Yoshida N, Yoshimi A, Villalobos IB, Hama A, Nishio N, Hidaka H, Wang Y, Yagasaki H, Kojima S.
  • 雑誌名: Leuk Res. 32 ページ: 1036-1042
• [雑誌論文] Acute megakaryoblastic leukaemia (AMKL) in children: a comparison of AMKL with and without Down syndrome (2008)
  • 著者名/発表者名: 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.
  • 雑誌名: Br J Haematol 140 ページ: 552-561
  • NAID: 120007138374
• [雑誌論文] 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)
  • 著者名/発表者名: 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
  • 雑誌名: Pediatr Transplant 12 ページ: 862-867
• [雑誌論文] Risk factors for early death in neonates with Down syndrome and transient leukaemia (2008)
  • 著者名/発表者名: Muramatsu H, Kato K, Watanabe N, Matsumoto K, Nakamura T, Horikoshi Y, Mimaya J, Suzuki C, Hayakawa M, Kojima S.
  • 雑誌名: Br J Haematol 142 ページ: 610-615
• [雑誌論文] 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)
  • 著者名/発表者名: 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.
  • 雑誌名: Br J Haematol Epub ahead of print
• [雑誌論文] Japanese epidemiological survey with consensus statement on Japanese guidelines for treatment of iron overload in bone marrow failure syndromes (2008)
  • 著者名/発表者名: Suzuki T, Tomonaga M, Miyazaki Y, Nakao S, Ohyashiki K, Matsumura I, Kohogo Y, Niitsu Y, Kojima S, Ozawa K.
  • 雑誌名: Int J Hematol 88 ページ: 30-35
  • NAID: 10025159021
• [雑誌論文] Japan Cord Blood Bank Network. Unrelated cord blood transplantation for severe aplastic anemia. Biol Blood Marrow Transplant (2008)
  • 著者名/発表者名: Yoshimi A, Kojima S, Tanigushi S, Hara J, Matsui T, Takahashi Y, Azuma H, Kato K, Nagamura-Inoue T, Kai S, Kato S
  • 雑誌名: Biol Blood Marrow Transplant 14 ページ: 1057-1063
• [雑誌論文] Congenital erythroid and myeloid hypoplasia terminating myelodysplastic syndrome (2008)
  • 著者名/発表者名: Nishio N, Yagasaki Y, Takahashi Y, Muramatsu H, Hama A, Zu Y, Villalobos IB, Kojima S.
  • 雑誌名: J Pediatr Hematol Oncol 30 ページ: 692-695
• [雑誌論文] 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)
  • 著者名/発表者名: Watanabe N, Matsumoto K, Yoshimi A, Horibe K, Matsuyama T, Kojima S, Kato K.
  • 雑誌名: Int J Hematol 88 ページ: 575-582
  • NAID: 10023971436
• [雑誌論文] Correlation of clinical features with the mutational status of GM-CSF signaling pathway-related genes in juvenile myelomonocytic leukemia (2008)
  • 著者名/発表者名: 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.
  • 雑誌名: Pediatr Res. [Epub ahead of print]
• [雑誌論文] Engraftment syndrome following allogeneic hematopoietic stem cell transplantation in children (2008)
  • 著者名/発表者名: Nishio N, Yagasaki H, Takahashi Y, Hama A, Muramatsu H, Tanaka M, Yoshida N, Yoshimi A, Kudo K, Ito M, Kojima S.
  • 雑誌名: Pediatr Transplant [Epub ahead of print]
• [雑誌論文] Prospective multicenter trial comparing repeated immunosuppre ssive therapy with stem-cell transplantation from an alternative donor as second-line treatment for children with severe and very severe aplastic anemia. (2008)
  • 著者名/発表者名: Kosaka Y, Kojima S, et al.
  • 雑誌名: Blood 111 ページ: 1054-1059
  • 査読あり
• [雑誌論文] Acute megakaryoblastic leukaemia (AMKL) in children : a comparison of AMKL with and without Down syndrorae. (2008)
  • 著者名/発表者名: Hama A, Kojima S, et al
  • 雑誌名: Br J Haematol 140 ページ: 552-661
  • 査読あり
• [雑誌論文] Quantification of granulocyte-macrophage colony-stimulating factor hypersensitivity in juvenile myelomonocytic leukemia by 3H-thymidine assay. (2008)
  • 著者名/発表者名: Tanaka M, Kojima S, et al.
  • 雑誌名: Leuk Res 32 ページ: 1036-1042
  • 査読あり
• [雑誌論文] Functional analysis of JAK3 mutations in transient myeloprolif erative disorder and acute megakaryoblastic leukaemia accompanying Down syndrome. (2008)
  • 著者名/発表者名: Sato T, Kojima S, et al.
  • 雑誌名: Br J Haematol 141 ページ: 681-688
  • 査読あり
• [雑誌論文] A conditioning regimen of busulfan, fludarabine, and melphalan for allogeneic stem cell transplantation in children with juvenile myelomonocytic leukemia. (2008)
  • 著者名/発表者名: Yabe M, Koiima S, et al.
  • 雑誌名: Pediatr Transplant 12 ページ: 862-867
  • 査読あり
• [雑誌論文] Congenital erythroid and myeloid hypoplasia terminating myelo dysplastic syndrome. (2008)
  • 著者名/発表者名: Nishio N, Kojima S, et al.
  • 雑誌名: J Pediatr Hematol Oncol 30 ページ: 692-695
  • 査読あり
• [雑誌論文] Unrelated cord blood transplantation for severe aplastic anemia (2008)
  • 著者名/発表者名: Yoshimi A, Kojima S, et al.
  • 雑誌名: Biol Blood Marrow Transplant 14 ページ: 1057-1063
  • 査読あり
• [雑誌論文] Japanese epidemiological survey with consensus statement on Japanese guidelines for treatment of iron overload in bone marrow failure syndromes. (2008)
  • 著者名/発表者名: Suzuki T, Kojima S, et al.
  • 雑誌名: Int J Hematol 88 ページ: 30-35
  • NAID: 10025159021
  • 査読あり
• [雑誌論文] 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)
  • 著者名/発表者名: Yoshida N, Kojima S, et al.
  • 雑誌名: Br J Haematol 3
  • 査読あり
• [雑誌論文] Risk factors for early death in neonates with Down syndrome and transient leukaemia. (2008)
  • 著者名/発表者名: Muramatsu H, Kojima S, et al.
  • 雑誌名: Br J Haematol 142 ページ: 610-615
  • 査読あり
• [雑誌論文] Engraftment syndrome following allogeneic hematopoietic stem cell transplantation in children. (2008)
  • 著者名/発表者名: Nishio N, Kojima S, et al.
  • 雑誌名: Pediatr Transplant 1
  • 査読あり
• [雑誌論文] Correlation of clinical features with the mutational status of G M-CSF signaling pathway-related genes in juvenile myelomonocytic leukemia. (2008)
  • 著者名/発表者名: Yoshida N, Kojima S, et al.
  • 雑誌名: Pediatr Res 26
  • 査読あり
• [雑誌論文] Mutational analysis of SOS1 gene in acute myeloid leukemia. (2008)
  • 著者名/発表者名: Tanizaki R, Kojima S, etal.
  • 雑誌名: Int J Hematol 88 ページ: 460-462
  • NAID: 10023970986
  • 査読あり
• [雑誌論文] Prospective multicenter trial comparing repeated immunosuppressive therapy with stem cell transplantation from an alternative donor as second-line treatment for with severe and very severe aplastic anemia. (2008)
  • 著者名/発表者名: Kosaka Y, Kojima S, et. al.
  • 雑誌名: Blood 111 ページ: 1054-1059
  • 査読あり
• [雑誌論文] Increased midkine gene expression in childhood B-precursor acute lymphoblastic leukemia. (2008)
  • 著者名/発表者名: Hidaka H, Kojima S, et. al.
  • 雑誌名: Leukemia Research 31 ページ: 1045-1051
  • 査読あり
• [雑誌論文] Pro-inflammatory cytokinemia is frequently found in Down syndrome patients with hematological disorders. (2008)
  • 著者名/発表者名: Shimada A, Kojima S, et. al.
  • 雑誌名: Leukemia Research 31 ページ: 1199-1203
  • 査読あり
• [雑誌論文] Increased midkine gene expression in childhood B-precursor acute lymphoblastic leukemia (2007)
  • 著者名/発表者名: 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.
  • 雑誌名: Leuk Res. 83 ページ: 535-540
• [雑誌論文] Spontaneous improvement of hematologic abnormalities in patients having juvenile myelomonocytic leukemia with specific RAS mutations (2007)
  • 著者名/発表者名: 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.
  • 雑誌名: Blood 109 ページ: 544-544
• [雑誌論文] Feasibility and results of bone marrow transplantation from an HLA-mismatched unrelated donor for children and young adults with acquired severe aplastic anemia (2007)
  • 著者名/発表者名: Yagasaki H, Takahashi Y, Kudo K, Ohashi H, Hama A, Yamamoto T, Tanaka M, Yoshida N, Hidaka H, Nishio N, Kojima S.
  • 雑誌名: Int J Haematol 85 ページ: 437-442
• [雑誌論文] Mutation of SBDS and SH2D1A is not associated with aplastic anemia in Japanese children (2007)
  • 著者名/発表者名: Wang Y, Yagasaki H, Hama A, Nishio N, Takahashi Y, Kojima S.
  • 雑誌名: Haematologica 92 ページ: 1573-1573
• [雑誌論文] 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)
  • 著者名/発表者名: 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
  • 雑誌名: J Clin Oncol 25 ページ: 5442-5447
• [雑誌論文] Japan Childhood Aplastic Anemia Study Group. Antithymocyte globulin and cyclosporine for treatment of 44 children with hepatitis associated aplastic anemia (2007)
  • 著者名/発表者名: Osugi Y, Yagasaki H, Sako M, Kosaka Y, Taga T, Ito T, Yamamoto M, Ohara A, Sato T, Mimaya J, Tsukimoto I, Kojima S
  • 雑誌名: Haematologica 92 ページ: 1687-1690
• [雑誌論文] Prospective study of a pirarubicin, intermediate-dose cytarabine and etoposide regimen in children with Down syndrome and acute myeloid leukemia. (2007)
  • 著者名/発表者名: Kudo K, Kojima S, et. al.
  • 雑誌名: J Cli Oncol 25 ページ: 5442-5447
  • 査読あり
• [雑誌論文] Antithymocyte globulin and cyclosporine for treatment of 44 children with hepatitis associated aplastic anemia. (2007)
  • 著者名/発表者名: Osugi Y, Kojima S, et. al.
  • 雑誌名: Haematologica 92 ページ: 1687-1690
  • 査読あり
• [雑誌論文] Spontaneous improvement of hematologic abnormalities in patients having juvenile myelomonocytic leukemia with specific RAS mutations. (2007)
  • 著者名/発表者名: Matsuda K, Kojima S, et. al.
  • 雑誌名: Blood 109 ページ: 5477-5480
  • 査読あり
• [学会発表] 再生不良性貧血における造血障害機序 : IFN-γは骨髄間葉系幹細胞のGATA-2の発現を低下させる (2008)
  • 著者名/発表者名: 徐銀燕, 小島勢二, 他
  • 学会等名: 日本血液学会
  • 発表場所: 京都
  • 年月日: 2008-10-11
• [学会発表] Bone Marrow Transplantation for Children with chronic myeloid leukemia (CML): A Report from the Japan Marrow Donor Program (JMDP) (2008)
  • 著者名/発表者名: Muramatsu H, Kojima S, et. al.
  • 学会等名: 50th Annual Meeting of the American Society of Hematology
  • 発表場所: Atlanta USA
• [学会発表] Predicting response to immunosuppressive therapy in childhood aplastic anemia (2008)
  • 著者名/発表者名: Yoshida N, Kojima S, et. al.
  • 学会等名: 50th Annual Meeting of the American Society of Hematology
  • 発表場所: Atlanta USA
• [学会発表] 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)
  • 著者名/発表者名: Hama A, Kojima S, et. al.
  • 学会等名: 50th Annual Meeting of the American Society of Hematology
  • 発表場所: Atlanta USA
• [学会発表] Myelodysplastic Syndrome (MDS) and myeloproliferative disease (MPD) in children: A Prospective registrarion of 222 Cases (2008)
  • 著者名/発表者名: Manabe A, Kojima S, et. al.
  • 学会等名: 50th Annual Meeting of the American Society of Hematology
  • 発表場所: Atlanta USA
• [学会発表] Mismatching at HLA-DPB1 is Not associated with survival in patients with acquired aplastic anemia who receive unrelated bone marrow transplantation (2008)
  • 著者名/発表者名: Yagasaki H, Kojima S, et. al.
  • 学会等名: 50th Annual Meeting of the American Society of Hematology
  • 発表場所: Atlanta USA
• [学会発表] Relapse of children with aplastic anemia after immunosuppressive therapy (2008)
  • 著者名/発表者名: Kamati Y, Kojima S, et. al.
  • 学会等名: 50th Annual Meeting of the American Society of Hematology
  • 発表場所: Atlanta USA
• [学会発表] Improved outcome of unrelated bone marrow transplantation for severe aplastic anemia (2008)
  • 著者名/発表者名: Yagasaki H, Kojima S, et. al.
  • 学会等名: 49th Annual Meeting of the American Society of Hematology
  • 発表場所: Atlanta USA
• [学会発表] Should hematopoietic stem cell transplantation in first complete remission be restricted to high-risk patients in childhood acute myeloid leukemia (2008)
  • 著者名/発表者名: Muramatsu H, Kojima S, et. al.
  • 学会等名: 49th Annual Meeting of the American Society of Hematology
  • 発表場所: Atlanta USA
• [学会発表] JAK3, JAK2 and GATA1 mutations in childhood acute megakaryoblastic leukemia with and without down syndrom (2008)
  • 著者名/発表者名: Hama A, Kojima S, et. al.
  • 学会等名: 49th Annual Meeting of the American Society of Hematology
  • 発表場所: Atlanta USA
• [学会発表] 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)
  • 著者名/発表者名: Takahashi Y, Kojima S, et. al.
  • 学会等名: 49th Annual Meeting of the American Society of Hematology
  • 発表場所: Atlanta USA
• [学会発表] Natural History of Transfusion-independent non-Severe Aplastic Anemia in Children (2008)
  • 著者名/発表者名: Nishio N, Kojima S, et. al.
  • 学会等名: 49th Annual Meeting of the American Society of Hematology
  • 発表場所: Atlanta USA
• [学会発表] Correlation of clinical features with the mutational status of GM-CSF signaling Pathway-related genes in children with juvenile myelomonocytic leukemia (2008)
  • 著者名/発表者名: Yoshida N, Kojima S, et. al.
  • 学会等名: 49th Annual Meeting of the American Society of Hematology
  • 発表場所: Atlanta USA
• [学会発表] Therapeutic strategies and clinical results in JMML-Update on Japanese trial (2008)
  • 著者名/発表者名: Kojima S
  • 学会等名: 2nd JMMLsymposium
  • 発表場所: Atlanta USA
• [学会発表] 再生不良性貧血の造血障害機序-骨髄間葉系細胞の関与 (2007)
  • 著者名/発表者名: 徐銀燕、小島勢二, 他
  • 学会等名: 日本血液学会総会
  • 発表場所: 横浜
  • 年月日: 2007-10-12
• [図書] 小児科第3版 (2008)
  • 著者名/発表者名: 小島勢二, 他
  • 出版者: 医学書院
• [図書] 小児科診療ガイドライン-最新の診療指針- (2007)
  • 著者名/発表者名: 小島勢二, 他
  • 出版者: 総合医学社