Tumor necrosis factor-α enhances DMSO-induced differentiation of HL-60 cells through the activation of ERK/MAPK pathway Authors
First Online: 08 February 2008 Received: 18 July 2007 Revised: 10 October 2007 Accepted: 19 November 2007 DOI:
Cite this article as: Yu, H., Lee, Y., Noh, E. et al. Int J Hematol (2008) 87: 189. doi:10.1007/s12185-008-0037-z Abstract
The differentiation of promyelocytic leukemic cells into mature cells is the major strategy for drug-based treatment of leukemia. Higher efficient methods to differentiate promyelocytic leukemic cells have been developed using various differentiation inducers including interferon-α, interleukin-4, tumor necrosis factor-α (TNF-α), and dimethyl sulfoxide (DMSO) as a single agent or in combination with each other. Here, we show that a combination of TNF-α with DMSO shows a synergic effect on HL-60 cell differentiation through the activation of ERK pathway. TNF-α enhanced CD11b expression and percent of cell population in the G
1 phase induced by DMSO, which are hallmarks for HL-60 cell differentiation. Inhibition of ERK pathway abolished the synergic effect of TNF-α in combination with DMSO on HL-60 differentiation, but the inhibition NF-κB pathway did not. These results suggest that TNF-α synergistically increases DMSO-induced differentiation of HL-60 cells through the activation of ERK/MAPK-signaling pathway. Keywords DMSO TNF-α MAPK NF-κB Leukemic cell differentiation References
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