Tumor Necrosis Factor-α Enhances DMSO-Induced Differentiation of HL-60 Cells through Activation of ERK/MAPK Pathway.

The differentiation of leukemic cells into mature cells is a major strategy for treatment of leukemia. Many trials for more efficient differentiation of leukemic cells have been performed using single uses of differentiation inducers including interferon-α (IFN-α), interleukin-4 (IL-4), tumor necrosis factor-α (TNF-α), and dimethyl sulfoxide (DMSO) or their combinations. Here we show that combination of TNF-α with DMSO enhances HL-60 cell differentiation. TNF-α enhanced DMSO-induced expression of CD11b and increase of G₁ phase in the cell cycle, which are hallmarks for HL60 cell differentiation. Inhibition of ERK pathway, but not NF-κB pathway, abolished the enhancement of DMSO-induced HL-60 differentiation by TNF-α. These results suggest that TNF-α enhances HL-60 cells towards induction of differentiation by DMSO through activation of ERK/MAPK signaling pathway.