Myeloid leukemia cell growth and differentiation are independent of mitogen-activated protein kinase ERK1/2 activation

The mitogen-activated protein kinase ERK1/2 pathway is essential in the con trol of cell proliferation and differentiation in most cellular systems. As such, it has been considered a potential target for antineoplastic therapy . For this purpose, we have examined the role of ERK activation in myeloid leukemia cell growth and differentiation. Using a representative set of mye loid leukemia cell lines, we show that cell proliferation was not accompani ed by increases on ERK1/2 activation, and mitogenic stimulation did not enh ance ERK activity. Moreover, abolition of ERK function by the inhibitor PD9 8059 or by a dominant inhibitory mutant ERK2 had no significant effects on proliferation. With the aid of various differentiation inducers, we found t hat within the same cell line, differentiation to a given lineage could occ ur with and without ERK1/2 activation, depending on the stimulus. Also, a d ifferentiator could have the same effect in the presence or absence of ERK stimulation, depending on the cell line. ERK inhibition did not affect the differentiation elicited by stimuli whose effects were accompanied by ERK a ctivation. Finally, constitutive ERK activity was also ineffective on proli feration and differentiation. Thus, our results indicate that ERK1/2 activa tion is not an essential requirement for leukemic cell growth and different iation.