Genetic abnormalities and immuno-therapy in juvenile myelogeneous leukemia

• Project/Area Number: 19790714
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Pediatrics
• Research Institution: Nagoya University
• Principal Investigator: YOSHIMI Ayami Nagoya University, 医学部, 寄附講座助教 (70432276)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,690,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,000,000 (Direct Cost: ¥2,000,000)
• Keywords: 若年性骨髄単球性白血病(JMML) / PTPN11 遺伝子 / RAS 遺伝子 / Wiskott-Aldrich 症候群 / 若年性骨髄単球性白血病 / PTPN 11遺伝子 / RAS遺伝子 / Wiskott-Aldrich症候群 / 若年性骨髓単球性白血病 / 顆粒球・マクロファージ刺激因子 / PTPN11遺伝子

Research Abstract

若年性骨髄単球性白血病(JMML)患者(71 例)の血液検体を用いてPTPN11、RAS、NF1 遺伝子の異常を検討し、それぞれ45%、16%、4%の患者において遺伝子異常を認めた。臨床所見および予後との相関を検討したところ、PTPN11 遺伝子異常のある患者は、診断時の年齢が高く、HbFが高値で、かつ生存率が低く、JMML の予後不良因子となると考えられた。
またJMML の疑いにて骨髄像の中央診断を受けた患者の中に、4 例の男児において先天性免疫不全症候群であるWiskott-Aldrich 症候群(WAS)をWASP 遺伝子検査およびWASP 蛋白のフォローサイトメトリー検査により診断した。WAS 患者においてJMML に類似した血液異常が認めうることが初めて明らかになった。
またJMML において、従来のコロニー方法に変わる、GM-CSF 過剰反応性の測定方法として (3)H-thymidine アッセイを用い方法を開発した。この方法は簡便でかつ定量的にGM-CSF 過剰反応性を測定でき、JMML の診断に有用であると考えられた。

Research Products

• [Journal Article] Juvenile Myelomonocytic Leukemia:Epidemiology and Management (2009)
  • Author(s): Yoshimi A, Kojima S, Hirano N
  • Journal Title: Considerations, Pediatric Drug
  • Peer Reviewed
• [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(1) Pages: 126-127
  • NAID: 10025159958
  • Peer Reviewed
• [Journal Article] Late-onset non-infectious pulmonary complications following allogeneic hematopoietic stem cell transplantation in children. Bone marrow Transplant (2009)
  • Author(s): Nisio N, Yagasaki H, Takahashi Y, Muramatsu H, Hama A, Tanaka M, Yoshida N, Watanabe N, Kudo K, Yoshimi A, Kojima S
  • Journal Title: Epub ahead of print
  • Peer Reviewed
• [Journal Article] The Activity of Hematopoietic Stem Cell Transplantation in Asia (2009)
  • Author(s): Yoshimi A, Suzuki R, Atsuta Y, Lu D-P, Ghavamzadeh A, Alimoghaddam K, Lie A, Liang R, Chan LL, Haipeng L, Tan PL Hwang WYK , Chiou TZ, Chen PM, Binh VT, Minh NN, Chang KM, Hwang TJ, Kodera Y
  • Journal Title: The Report from the Asian Pacific Blood and Marrow Transplantation Group
  • Peer Reviewed
• [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, Kojima S
  • Journal Title: Pediatr Res 65 Pages: 334-340
  • Peer Reviewed
• [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(7) Pages: 1036-1042
  • Peer Reviewed
• [Journal Article] Al, Unrelated cord blood transplantation for severe aplastic anemia (2008)
  • Author(s): Yoshimi A, Kojima S, Taniguchi S
  • Journal Title: Biol Blood Marrow Transplant 14 Pages: 1057-1063
  • Peer Reviewed
• [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
  • Peer Reviewed
• [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(5) Pages: 575-582
  • NAID: 10023971436
  • Peer Reviewed
• [Journal Article] International Working Group on Morphology of Myelodysplastic Syndrome. Diagnosis and classification of myelodysplastic syndrome: International Working Group on Morphology of myelodysplastic syndrome (IWGM-MDS) consensus proposals for the definition and enumeration of myeloblasts and ring sideroblasts (2008)
  • Author(s): Mufti GJ, Bennett JM, Goasguen J, Bain BJ, Baumann I, Brunning R, Cazzola M, Fenaux P, Germing U, Hellstrom-Lindberg E, Jinnai I, Manabe A, Matsuda A, Niemeyer CM, Sanz G, Tomonaga M, Vallespi T, Yoshimi A
  • Journal Title: Haematologica 93(11) Pages: 1712-1717
  • Peer Reviewed
• [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: syndrome.Br J Haematol 140(5) Pages: 552-561
  • NAID: 120007138374
  • Peer Reviewed
• [Journal Article] Juvenile Myelomonocytic Leukemia : Epidemiology and Management Considerations (2008)
  • Author(s): Yoshimi A, Kojima S, Hirano N
  • Journal Title: Pediatric Drug (印刷中)
  • Peer Reviewed
• [Journal Article] Unrelated cord blood transplantation for severe aplastic anemia (2008)
  • Author(s): Yoshimi A, Kojima S, Taniguchi S, et.al.
  • Journal Title: Biol Blood Marrow Transplant 14 Pages: 1057-63
  • Peer Reviewed
• [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: 552-61
  • NAID: 120007138374
  • Peer Reviewed
• [Journal Article] Quantification of granulocyte -macrophage colony -stimulating factor hypersensitivity in juvenile myelomonocytic leukemia by 3 H-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: 1036-42
  • Peer Reviewed
• [Journal Article] Juvenile Myelomonocytic Leukemia: Epidemiology and Management Considerations (2008)
  • Author(s): Ayami Yoshimi, Seiji Kojima and Naoto Hirano
  • Journal Title: Pediatric Drugs (In press)
  • Peer Reviewed
• [Journal Article] Wiskott-Aldrich syndrome is an important differential diagnosis in male infants with juvenile myelomonocytic leukemialike features (2007)
  • Author(s): Watanabe N, Yoshimi A, Kamachi Y, Kawabe T, Muramatsu H, Matsumoto K, Manabe A, Kojima S, Kato K.
  • Journal Title: J Pediatr Hematol Oncol 9(12) Pages: 836-838
  • Peer Reviewed
• [Journal Article] Wiskott-Aldrich syndrome is an important differential diagnosis in maleinfants with juvenile myelomonocytic leukemia-like features (2007)
  • Author(s): Nobuhiro Watanabe, Ayami Yoshimi, Yoshiro Kamachi, Takashi Kawabe, Hideki Muramatsu, Kimikazu Matsumoto, Atsushi Manabe, Seiji Kojima, Koji Kato
  • Journal Title: J Pediatr Hematol Oncol. 29(12) Pages: 836-8
  • Peer Reviewed
• [Presentation] 骨髄異形成症候群・骨髄増殖性疾患用の臨床像を合併したWiskott-Aldrich 症候群 (2008)
  • Author(s): 吉見礼美
  • Organizer: 第一回免疫不全研究会
  • Place of Presentation: 東京
  • Year and Date: 2008-01-19
• [Presentation] 骨髄異形成症侯群・骨髄増殖性疾患用の臨床像を合併したWoskott-Aldrich症候群 (2008)
  • Author(s): 吉見礼美, ら
  • Organizer: 第一回免疫不全研究会
  • Place of Presentation: 東京
  • Year and Date: 2008-01-19