Research Project
Grant-in-Aid for Scientific Research (C)
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.
All 2007 2006
All Journal Article (7 results) (of which Peer Reviewed: 2 results)
Cancer Research 67
Pages: 9851-9861
Cancer Res 67
Leukemia 21
Pages: 288-296
Leukemia 20
Pages: 363-365
Pages: 2119-2129
Brit H Haematol 135
Pages: 410-411