Analysis of the FLT3/FLT3 ligand system in ALL with 11q23 translocations

• Project/Area Number: 18591187
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: University of Yamanashi
• Principal Investigator: SUGITA Kanji University of Yamanashi, Department of Research Interdisciplinary Graduate School of Medicine and Engineering, Professor (60138055)
• Co-Investigator(Kenkyū-buntansha): INUKAI Takeshi University of Yamanashi, Hospital, Assistant Professor (30293450) ; GOI Kumiko University of Yamanashi, Department of Research Interdisciplinary Graduate School of Medicine and Engineering, Research Associate (70324192)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥3,590,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
• Keywords: FLT3 / FLT3 ligand / ALL / 11q23 tralslocations

Research Abstract

Mechanism of the FLT3 ligand (FL) -induced cell cycle arrest and acquisition of resistance against anti-leukemic drugs in ALL with 11q23 translocations was analyzed. Three days after culture in the presence of FL, KOCL-58 cell line with 11q23 translocation was induced into GO/GI arrest with up-regulation of CDK inhibitor p27 and dephosphorylation of STATS. In FL-induced cell cycle arrest, the cell line showed resistance against daunorubicin (DNR) or cytosine arabinosid (AraC). When cocultured with bone marrow stromal cell line expressing membrane-bound form of FL at high levels, the cell line was induced into GO/GI arrest and showed resistance to DNR or AraC. This effect was partially abrogated in the presence of anti-FL antibody. Thus, ALL cells with 11q23 translocations are induced into quiescent state resistant to chemotherapy in vivo when they adhere to bone marrow stromal cells producing FL irrespective of membrane-bound form or secretary form. This FLT3/FL system may be associated with the formation of minimum residual disease in bone marrow resulting in early relapse of ALL with 11q23 translocations.

Research Products

• [Journal Article] Fms-like kinase 3 ligand stimulation induces MLL-rearranged leukemia cells into quiescence resistant to antileukemic agents. (2007)
  • Author(s): Furuichi Y. Goi K, Inukai T, Sato H, Nemoto A, Takahashi K, Akahane K, Hirose K, Honna H, Kuroda I, Zhang X, Kagami K, Hayashi Y, Harigaya K, Nakazawa S, Sugita K
  • Journal Title: Cancer Research 67 Pages: 9851-9861
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Fms-like kinase 3 ligand stimulation induces MLL-rearranged leukemia cells into quiescence resistant to antileukemic agents (2007)
  • Author(s): Furuichi, Y., Goi, K., Inukai, T., Sato, H., Nemoto, A., Takahashi, K., Akahane, K., Hirose, K., Hanna, H., Kuroda, I., Zhang, X., Kagami, K., Hayashi, Y., Harigaya, K., Nakazawa, S., Sugita, K
  • Journal Title: Cancer Research 67 Pages: 9851-9861
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Fms-1ike kinase 3 1igand stimulation induces MLL-rearranged leukemia cells into quiescence resistant to antileukemic agents. (2007)
  • Author(s): Furuichi Y. Goi K, Inukai T, Sato H, Nemoto A, Takahashi K, Akahane K, Hirose K, Honna H, Kuroda I, Zhang X, Kagami K, Hayashi Y, Harigaya K, Nakazawa S, Sugita K
  • Journal Title: Cancer Res 67 Pages: 9851-9861
  • Peer Reviewed
• [Journal Article] Hypercalcemia in childhood acute lymphobastic leukemia : inplication of PTHrP and frequent presence of the E2A-HLF from translocation 17;19. (2007)
  • Author(s): Inukai T, Sugita K, et al.
  • Journal Title: Leukemia 21 Pages: 288-296
• [Journal Article] Clonotypic analysis of acute lymphoblastic leukemia with a double TEL/AML1 fusion at onset and relapse. (2006)
  • Author(s): Inukai T, Goi K, Sugita K, et al.
  • Journal Title: Leukemia 20 Pages: 363-365
• [Journal Article] Resistance of infant leukemia with MLL rearrangement to tumornecrosis factor-related apoptosis-inducing ligand : a possible mechanism for poor sensitivity to antitumor immunity. (2006)
  • Author(s): Inukai T, Goi K, Sugita K, et al.
  • Journal Title: Leukemia 20 Pages: 2119-2129
• [Journal Article] Natural pregnancy and delivery after bone marrow transplantation in a Fanconi anemia patient. (2006)
  • Author(s): Goi K, Sugita K, Inukai T, et al.
  • Journal Title: Brit H Haematol 135 Pages: 410-411