CpG Oligodeoxynucleotides Induced Monocytic Differentiation Of Leukemia Cells And Signal Transduction Pathway Of CpG ODN In The Activated Dendritic Cell

CpG ODN is defined as DNA molecules containing unmethylated CpG- dinucleotides flanked by two 5?purines and two 3?primidines. They can activate antigen- presenting cells (APCs) including B cells, macrophages, and dendritic cells (DC s). CpG ODN also indirectly activates T cells and preferentially promotes Thl immune response. Because of its potent ability to induce secretion of IL-12 and lEN-gamma, which are Thl cytokines, CpG ODN is widely investigated as a potential adjuvant in the treatment of cancer, infection disease, and allergic disease. Part I: CpG ODN induces monocyte differentiation and apoptosis of FBL-3 leukemia cells One of the strategies in treating patients with leukemia is to induce differentiation or apoptosis of tumor cells, which has been considered as a prospective approach in leukemia immunotherapy. Myelogenous or lymphoblastic leukemia cells can be further induced to differentiate into granulocytes, monocyteslmacrophages, and dendritic cells by many agents, such as all-trans retinoic acid, phorbol 1 2-myri state 13-acetate, vitamin D derivatives and certain cytokines. CpG ODN can enhance the therapeutic efficacy of monoclonal antibody, augment immunogenicity of tumor-associated antigen or DNA vaccine. Although it has been shown that CpG ODN may activate immune system to eliminate tumor cells, it is barely known whether CpG ODN by itself can affect tumor cells. So we investigated whether CpG can induce differentiation of leukemia cells. Recently, it has been observed that CpG ODN could increase the expression of MHC and co-stimulatory molecules on the surface of chronic lymphocytic leukemia B cells, which have strong capacity to stimulate allogeneic T cells in mixed lymphocyte reaction (M1LR). Our previous work has shown that murine erythroid leukemia FBL-3 cells could be induced to differentiate into monocytes and DCs by GM-CSF, resulting in enhanced antigen presenting function. Here we used this FBL-3 leukemia cell model to explore whether CpG ODN can induce differentiation of mouse erythroid leukemia cells. We showed herein that CpG ODN could dose-dependently inhibit the growth of FBL-3 cells as measured by MIT reduction assay. The inhibition rate was 54.72% with 4p.M CpG ODN. Treatment of FBL-3 with 2pM CpG ODN for 72h induced cellular morphological change and de novo expression of CD14 (MFI 37.94 vs. 0.30 p