Wilms tumor gene(WT1)expression in leukemic and normal hematopoietic stem cells.

• Project/Area Number: 09671110
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Osaka University
• Principal Investigator: OGAWA Hiroyasu Osaka University Medical School, Associate Professor, 医学部, 助教授 (80194447)
• Co-Investigator(Kenkyū-buntansha): TATEKAWA Toyoshi Osaka University Hospital, Medical Staff, 医学部・附属病院, 医員 ; OJI Yusuke Osaka University Medical School, Assistant Professor, 医学部, 助手 (20294100) ; SOMA Toshihiro Osaka University Medical School, Assistant Professor, 医学部, 助手 (40273619) ; OKA Yoshihiro Osaka University Medical School, Assistant Professor, 医学部, 助手 (20273691) ; 三宅 正剛 大阪大学, 医学部, 助手 (60294097)
• Project Period (FY): 1997 – 1998
• Project Status: Completed (Fiscal Year 1998)
• Budget Amount: ¥3,000,000 (Direct Cost: ¥3,000,000); Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000); Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: WT1 gene / minimal residual disease / hematopoietic stem cell / Leukemia / WT1 / 微小残存白血病 / 骨髄移植

Research Abstract

As Wilms' tumor gene (WT1) is highly expressed in bone marrow and blood specimens in all patients with leukemia, minimal residual leukemia (MRD) can be estimated by the quanlitation of the gene expression with RT-PCR method.Low level expression of WT1 gene in CD34 fraction of normal bone marrow cells may result in reducing the sensitivity of the detection of MRD by WT1 assay.In allogeneic bone marrow transplantation setting, CD34 fraction and WT1 levels of the bone marrow cells were monitored in patients with lymphoma who did not expressed WT1 gene.As a result, the percentage of the normal CD34 fraction and WT1 gene expression level derived from the fraction concurrently decreased to less than one tenth.On the other hand, WT1 gene expression in leukemic cells is increased in relapse.Therefore, this MRD detection system is very useful for the diagnosis of early molecular relapse in patients with leukemia who were treated with bone marrow transplantation.

Research Products

• [Publications] Ogawa H,,et al.: "Successful donor leukocyte transfusion at molecular relapse for a patient with acute myeloid leukemia who was treated with allogeneic bone marrow transplantation : Importance of the monitoring. of minimal residual disease by WT1 assay." Bone Marrow Transplantation. 21. 525-527 (1998)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Inoue K.,et al.: "Wilms' tumor gene (WT1) competes with differentiation-inducing signal in hematopoietic progenitor cells." Blood. 91. 2969-2976 (1998)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Sako M.,et al.: "Abnormal expression of the Wilms' tumor gene WT1 in juvenile chronic myeloid leukemia and infantile monosomy 7 syndrome." Leukemia Research,. (in press.).
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tamaki H.,et al.: "The Wilms' tumor gene WT1 is a good marker for diagnosis of disease progression of myelodysplastic syndromes." Leukemia,. (in press).
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tsuboi A.,et al.: "Constitutive expression of the Wilms' tumor gene WT1 inhibits the differentiation of myeloid progenitor cells but promotes their proliferation in response to granulocyte-colony stimulating factor (G-CSF)." Leukemia Research.(in press).
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Oji Y.,et al.: "Expression of the Wilms' tumor gene WT1 in solid tumors and its involvement in tumor cell growth." Japanese Journal of Cancer Research,. (in press).
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ogawa H,Tsuboi A,Oji Y,Tamaki H,Soma T,Inoue K and Sugiyama H.: "Successful donor leukocyte transfusion at molecular relapse for a patient with acute myeloid leukemia who was treated with allogeneic bone marrow transplantation : Importance of the monitoring of minimal residual disease by WT1 assay." Bone Marrow Transplantarion. 21. 525-527 (1998)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Inoue K,Tamaki H,Ogawa H,Oka Y,Soma T,Tatekawa T,Oji Y,Tsuboi A,Kim EH,Kawakami M,Akiyama T,Kishimoto T,and Suigyama H.: "Wilms'tumor gene(WT1)competes with differentiation-inducing signal in hematopoietic progenitor cells." Blood. 91. 2969-2976 (1998)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Sako M,Ogawa H,Okamura J,Tamaki H,Nakahata T,Kishimoto T,and Sugiyama H.: "Abnormal expression of the Wilms'tumor gene WT1 in juvenile chronic myeloid leukemia and infantile monosomy 7 syndrome." Leukemia Research. (in press).
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tamaki H,Ogawa H,Ohyashiki K,Oyhashiki JH, Iwama H,Inoue K,Soma T,Oka Y,Tatekawa T,Oji Y,Tsuboi A,Kim EH,Kawakami M,Fuchigami K,Tomonaga M,Toyama K,Aozasa K,Kishimoto T,and Sugiyama H.: "The Wilms' tumor gene WT1 is a good marker for diagnosis of disease progression of myelodysplastic syndromes." Leukemia. (in press).
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tsuboi A,Oka Y,Ogawa H,Elisseeva AA,Tamaki H,Oji Y,Kim EH,Soma T,Tatekawa T,Kawakami M,Kishimoto T,and Sugiyama H.: "Constitutive expression of the Wilms'tumor gene WT1 inhibits the differentiation of myeloid progenitor cells but promotes their proliferation in response to granulocyte-colony stimulating factor (G-CSF)." Leukemia Research. (in press).
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Oji Y,Ogawa H,Tamaki H,Oka Y,Tsuboi A,Kim EH,Soma T,Tatekawa T,Kawakami M,Asada M,Kishimoto T,and Sugiyama H.: "Expression of the Wilms'tumor gene WT1 in solid tumors and its involvement in tumor cell growth." Japanese Journal of Cancer Research.
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ogawa H,,et al.: "Successful donor leukocyte transfusion at molecular relapse for a patient with acute myeloid leukemia who was treated with allogeneic bone marrow transplantation: Importance of the monitoring of minimal residual disease by WT1 assay." Bone Marrow Transplantation. 21. 525-527 (1998)
• [Publications] Inoue K.,et al.: "Wilms'tumor gene(WT1)competes with differentiation-inducing signal in hematopoietic progenitor cells." Blood. 91. 2969-2976 (1998)
• [Publications] Sako M.,et al.: "Abnormal expression of the Wilms'tumor gene WT1 in juvenile chronic myeloid leukemia and infantile monosomy 7 syndrome." Leukemia Reseaech. in press.
• [Publications] Tamaki H.,et al.: "The Wilms'tumor gene WT1 is a good marker for diagnosis of disease progression of myelodysplastic syndromes." Leukemia,. in press.
• [Publications] Tsuboi A.,et al.: "Constitutive expression of the Wilms'tumor gene WT1 inhibits the defferentiation of myeloid progenitor cells but promotes their proliferation in response to granulocyte-colony stimulating factor(G-CSF)." Leukemia Research. in press.
• [Publications] Oji Y.,et al.: "Expression of the Wilms'tumor gene WT1 in solid tumors and its involvement in tumor cell growth." Japanease Journal of Cancer Research. in press.
• [Publications] Yamagami T.: "Suppression of Wilms' tumor gene (WT1) expression induces G_2/M arrest in leukemic cells." Leukemia Research. (in press.).
• [Publications] Sugiyama H.: "Wilms tumor gene (WT1) mRNA is equally expressed in blast cells from acute myeloid leukemia and normal CD34+ progenitors (Response)." Blood. (in press.).
• [Publications] Inoue K.: "Wilms' tumor gene (WT1) competes with differentiation-inducing signal in hematopoietic progenitor cells." Blood. (in press.).
• [Publications] Ogawa H.: "Successful donor leukocyte transfusion at molecular relapse for a patient with asute myeloid leukemia who was treated with allogeneic bone marrow transplantation : Importance of the monitoring of minimal residual disease by WT1 assay." Bone Marrow Transplantation. (in press.).
• [Publications] Ogawa H.: "A high incidence of chemotherapy-induced acral erythema (CAE) in female patients with non-Hodgkin's lymphoma who were treated with VACOP-B regimen." Leukemia and Lymphoma. (in press.).