CONSTITUTIVE EXPRESSION OF EXOGENOUS C-MYB GENE CAUSES MATURATION BLOCK IN MONOCYTE-MACROPHAGE DIFFERENTIATION

A nuclear protooncogene c-myb has been hypothesized to play an important role in hematopoiesis, but little is known about the physiological function of the c-myb gene products. To study the role of c-myb gene expression in monocyte-macrophage differentiation and proliferation, we introduced exogenous c-myb gene into murine myelomonocytic leukemia WEHI-3B(D +) cells which can be induced to differentiate into mature monocytes with granulocyte-colony stimulation factor (G-CSF) and actinomycin D. Expression of the transfected gene was found to result in elevated levels of c-myb transcripts, which were not subject to normal down-regulation by differentiation induction. This constitutive expression of c-myb gene allowed the c-myb transfectants to differentiate into promonocytes with G-CSF and actinomycin D, but blocked further maturation from promonocytes to mature monocytes. It is concluded that normal down-regulation of c-myb gene expression during monocyte-macrophage differentiation is required for the maturation of promonocytes to mature monocytes.