The activity of extracellular signal-regulated kinase is required during G2/M phase before metaphase-anaphase transition in synchronized leukemia cell lines

The pharmacological inhibitors of extracellular signal-regulated kinase (ERK) have been suggested as a novel molecular target-based therapy for acute myeloid leukemia. Several studies have established the role of ERK in cell cycle progression from G1 to S phase in response to mitogen, but the role of ERK after the restriction point is less clarified. In this study, we used models of aphidicolin and nocodazole-synchronized HL-60 and NB4 leukemia cell lines to determine the kinetics of ERK activity during the progression of the cell cycle and to test the effects of commercially available inhibitors on G2/M progression of synchronized leukemia cells. In aphidicolin-synchronized cells, the activity of ERK was low during early S phase and increased at late S and G2/M phase of the cell cycle. The presence of MEK inhibitors PD 98059 and U0126 caused a delay in G2/M phase. In nocodazole-synchronized cells, the activity of ERK was low during M/G1 transition and MEK inhibitors had no effects on return of the cells to G1 phase. These results demonstrate that the activity of ERK is required during G2/M phase of leukemia cell cycle before the cells reach metaphase–anaphase transition.