| Acute myeloid leukemia(AML)is a clonal and heterogeneous disease characterized by a myriad of genetic defects. These include translocations involving oncogenes and transcription factors, activation of signal transduction pathways, and alterations of growth factor receptors. Progress in therapy and supportive care over the past three decades has led to gradual improvement in the overall results, but the majority of patients will die from their disease. If each type of genetic lesion found in AML involved a distinct process to cause leukemia, then "targeted" therapy directed at specific genetic lesions would be futile—quite simply, there would be too many potential targets. However, it appears that many of the pathways perturbed in leukemogenesis interact, so that a limited number of specific targets may be useful in a wide variety of AML cases. Indeed, if multiple genetic abnormalities are needed to cause and sustain AML, then the blunting of a single aberrant pathway may be enough to eliminate the proliferative advantage and curb the disease. A better understanding of the biology of AML may facilitate the development of a selective therapy that exploits specific biological properties.The mammalian thioredoxins are a family of small (approximately 12 KDa) redox proteins that undergo NADPH-dependent reduction by thioredoxin reductase and in turn reduce oxidized cysteine groups on proteins. Thioredoxins (Trxs) have a conserved catalytic site (-Trp-Cys-Gly-Pro-Cys-Lys-) that undergoes reversible oxidation to the cystine disulfide (Trx-S2) through the transfer of reducing equivalents from the catalytic site cysteine residues (Cys) to, typically, a disulfide substrate (X-S2). The oxidized Trx is then reduced back to the Cys form [Trx-(SH)2] by the NADPH- dependent flavoprotein thioredoxin reductase.Thioredoxin is a new identified cancer protein. The thioredoxin levels showed a highly significant positive correlation with cancers. Studies with a variety of human primary tumors have shown that thioredoxin is overexpressed in the tumor compared to levels in the corresponding normal tissue. Furthermore, high levels of thioredoxin in the tumor appear to be associated with decreased patient survival. On the other hand, thioredoxin has many other biological activities, such as antioxidant properties, protective effect against reperfusion, chemotaxic effects. It plays protective roles in atherosclerosis, interstitial lung disease and developing embryo. But the role of thioredoxin in AML is now unknown. It is interesting to investigate the relationship between thioredoxin and AML.We investigated the expression of thioredoxin in AML and studied its therapeutic implication. Firstly, we examined the expression of thioredoxin in AML using Western Blotting and studied its clinical implication through its relationship with the count of white blood cells, the primary cells in bone marrow, complete remission rate and survival. Then dendritic cells (DCs) derived from peripheral blood mononuclear cells (PBMNCs) of the patients with AML in complete remission were cultured for 7 days in RPMI 1640 media system composed of human AB serum, GM-CSF, rhIL-4, and/no rhCD40L. Some of the cell suspensions were fixed and stained with Wright-Giemsa stain. Cell morphology was determined by light microscope and inverse light microscope. Some cell suspensions were fixed followed by flow cytometry to analyze the phenotype. The functions of the DCs were determined by mixed lymphocytic reaction (MLR) and IL-12 secretion using MTT and ELISA. The synthesization and secretion of thioredoxin in thioredoxin-positive AML-CR/DCs was examined by Western Blotting and MTT assay. Thioredoxin inhibitor was used to analyze the effects of thioredoxin on the activation of T cells provided by DCs. Finally, the effects of thioredoxin inhibitor on the growth and apoptosis of AML primary cells were measured with morphological observation, DNA electrophoresis and MTT assay. To be important, the focus was on demonstrating whether thioredoxin had a pot...
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