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

2007 Fiscal Year Final Research Report Summary

• 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
• 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