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 G(1) 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 G(2)/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 G(2)/M phase of the cell cycle. The presence of
MEK inhibitors
PD 98059 and
U0126 caused a delay in G(2)/M phase. In
nocodazole-synchronized cells, the activity of ERK was low during M/G(1) transition and
MEK inhibitors had no effects on return of the cells to G(1) phase. These results demonstrate that the activity of ERK is required during G(2)/M phase of
leukemia cell cycle before the cells reach metaphase-anaphase transition.