Overcoming TNF-αInduced Suppression of Erythroid Differentiation of Human Cord Blood CD34+ Cells with Arsenic Trioxide.

The anemia of chronic disease-which encompasses inflammation, infection, tissue injury, and conditions associated with the release of proinflammatory cytokines (such as cancer)- is one of the most common forms of anemia seen clinically. Symptomatic anemia requires treatment. The two major forms of treatment are transfusions and erythropoietin. Arsenic trioxide (As2O3) used to treat human diseases for centuries in traditional Chinese medicine. Our recent studies suggest that low dose of As2O3induces erythroid differentiation of K562 human leukemic cells and high dose of As2O3induce apoptosis. In this study, we have investigated in vitro effect of As2O3on the erythroid differentiation and it could inhibit TNF-αinduced suppression of erythroid differentiation of human cord blood CD34+ cells. Expression of glycophorin A was 35.94 ± 7.94% after 7 days culture of human cord blood CD34+ cells and was decreased to 17.63 ± 7.33% when culture of human cord blood CD34+ cells with 100ng/mL of TNF-α. Expression of glycophorin A was increased in dose dependent manner after 7 days treatment with As2O3and As2O3increased percentage of glycophorin A in culture with TNF-αcompared to TNF-αalone. The results of colony assay of CFU-MIX and BFU-E after culture with various conditions revealed similar patterns with expression of glycophorin A. These results suggest that As2O3induces erythroid differentiation of human cord blood CD34+ cells and can reverse TNF-αinduced suppression of erythroid differentiation of human cord blood CD34+ cells.