Basic study of the origin of dendritic cells and their thrapeutic application in Ph(+)-chronic myelogenous leukemia

• Project/Area Number: 09671095
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: The University of Tokyo
• Principal Investigator: TOJO Arinobu The University of Tokyo, Insitute of Medical Science, Lecturer, 医科学研究所, 講師 (00211681)
• Co-Investigator(Kenkyū-buntansha): SATO Yuko Research Institute, Chief Investigator International Medical Center of Japan, 室長 (10137713) ; ASANO Shigetaka The University of Tokyo, Insitute of Medical Science, Professor, 医科学研究所, 教授 (50134614)
• Project Period (FY): 1997 – 1998
• Project Status: Completed (Fiscal Year 1998)
• Budget Amount: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 1998: ¥1,600,000 (Direct Cost: ¥1,600,000); Fiscal Year 1997: ¥1,900,000 (Direct Cost: ¥1,900,000)
• Keywords: CML / Dendritic Cell / Ph Chromosome / Dendritic cell (樹状細胞) / 慢性骨髄性白血病(CML) / フィラデルフィア染色体(Ph) / 樹状細胞(DC)

Research Abstract

Chronic myelogenous leukemia (CML) is a myeloprolilerative disorder resulting from a single hematopoietic stem cell carrying Philadelphia (Ph) chromosome. A recent series of studies have suggested that CML cells can be immunogenic to autologous T cells which are usually not involved in Ph clone. Dendritic cells (DCs) are the most efficient antigen-presenting cells and derived from CD34^+ progenitor cells, which were retrospectively identified as DC-colony forming cells in a semisolid culture. We performed comparative analysis of DC colony forming unit (CFU-DC) between normal subjects and patients with CML.Bone marrow CD34^+ cells purified by immunomagnetic beads were cultured in a methylcellulose medium containing stem cell factor, granulocyte-macrophage colony stimulating factor, tumor necrosis factor-a with or without interleukin-4, which proved to stimulate the growth of CFU-DC.The amount of CFU-DC was evaluated as the number of DC colonies per 10 granulocyte-macrophage colonies simultanously assayed in the presence of multiple cytokine cocktails. CML patients revealed the significantly lower amount of CFU-DC than normal subjects (1.5*1.8 [n=10] vs 4.1*1.6 [n=6], p<0.01). Cytogenetic analysis of individual DC colonies from 3 CML patients demonstrated the presence of Ph chromosome in all the metaphases analysed. Reverse transcription polymerase chain reaction analysis confirmed the expression of BCR-ABL mRNA as well as CD83 mRNA in DC colony forming cells, implying the possible application of CML DCs to elicit Ph-specific T cell responses.

Research Products

• [Publications] Tsujimuro H,Sato Y,Asano S,and Tojo A: "The clonal origin and the relative decrease in number of bone marrow dendritic cell colony-forming unit in chronic myelogenous leukeuis." Blood. in press. (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tsujimura H,Tojo A,Watari K,Tani K,Sato Y,and Asano S: "Comparative analysis of peupherel blood dendrific cells and their bone marrow progenitor cellls between normal subjects and patients with CML" Blood. 90. 83a (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tsujimura H,Sato Y,Asano S,and Tojo A.: "The Clonal origin and the relativedecrease in number of bone marrow dendritic cell colony-forming unit in chronic myelogenous leukemia" Blood. (in press). (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tsujimura H,Tojo A,Watari K,Tani K,Sato Y,and Asano S.: "Comparative analysis of peripheral blood dendritic cells and their bone marrow progenitor cells between normal subjects and patients with CML." Blood. 90. 83a (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tsujimura H,Sato Y,Asano S,and Tojo A: "The clonal origin and the relative decrease in numbor of bone narrow dendritic cell colony-frming unit in drruie myelogenous lenkania." Blood (in press). (1999)
• [Publications] Tsujimura H,Tojo A,Watari K,Tani K,Sato Y,and Asano S.: "Comparative analysis of perpherd blood dendritic cells and their bone marrow progenitor cells between normal subjects and patients with CML." Blood. 90. 83a (1997)
• [Publications] H.Tsujimura et al: "Comparative analysis of peripheral blood dendutic cells and their from marrow progenitor cells between normal subjects and patients with CML." BLOOD. 90・10. 83a (1997)