OBJECTIVETo investigate the effects of ST1571 on the development of dendritic cells (DC) derived from bone marrow mononuclear cells of patients with chronic myeloid leukemia (CML).

METHODSBone marrow mononuclear cells (BMMNC) from CML patients and healthy volunteers were cultured initially using multiple cytokine combinations as follows: recombinant human granulocyte/ macrophage colony-stimulating-factor (rhGM-CSF) plus recombinant human interleukin-4 (rhIL-4) as CML and normal control groups, rhGM-CSF plus rhIL-4 and ST1571 as CML experimental groups, and from day 8 recombinant human tumor necrosis factor-alpha ( rhTNF-alpha) was added to stimulate DC maturation. The morphologic features of cells were observed by Wright's staining and phenotypes were assessed by flow cytometry. Cytogenetic analysis was performed by fluorescence in-situ hybridization (FISH), and the antigen-presenting function was assayed by mixed lymphocyte reaction (MLR). The concentration of VEGF was detected by ELISA.

RESULTSCML experimental groups treated with STI571 displayed morphological features similar to those of control groups with delicate membrane projections. However, in comparison with the CML control groups, the CML experimental groups showed an increased expression of CD80, CD86, CD83 and HLA-DR and showed more intense abilities of allogeneic antigen presentation, which were similar to those of normal control groups. FISH confirmed that DCs of both CML, groups were of leukemic origin. The concentration of VEGF was dramatically reduced in CML experimental groups.

CONCLUSIONIn vitro, STI571 promotes the activation/maturation of DCs derived from BMMNCs of patients with CMI, and decreases VEGF production by the leukemic cells. The promotion of DC maturation may be partially due to decreased inhibitory effect of VEGF.

Adult ; Antigens, CD ; metabolism ; Benzamides ; Bone Marrow Cells ; drug effects ; metabolism ; pathology ; Cell Proliferation ; drug effects ; Cells, Cultured ; Dendritic Cells ; drug effects ; metabolism ; pathology ; Female ; Flow Cytometry ; Fusion Proteins, bcr-abl ; genetics ; metabolism ; HLA-DR Antigens ; metabolism ; Humans ; Imatinib Mesylate ; In Situ Hybridization, Fluorescence ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; blood ; pathology ; Male ; Middle Aged ; Piperazines ; Pyrimidines ; pharmacology ; T-Lymphocytes ; drug effects ; metabolism ; pathology ; Vascular Endothelial Growth Factor A ; metabolism