Correlation between the induction of leukemic cell differentiation by various retinoids and modulation of protein...

During retinoic acid induced differentiation of the human promyelocyte leukemia cell line HL60 and the human myeloblast cell line RDFD along the myeloid pathway, there is marked modulation of both the cyclic adenosine 3':5'-monophosphate dependent protein kinase and the phospholipid-sensitive calcium dependent protein kinase. In order to further assess whether these kinases are intimately associated with the differentiation process, we have correlated the modulation of these enzymes and phosphorylations of their substrates with the extent of differentiation induced by various retinoid derivatives. We observed that there was a direct relationship between the degree of differentiation of the two leukemic cell lines and the elevation of the cyclic adenosine 3':5'-monophosphate dependent protein kinase and phospholipid sensitive calcium dependent protein kinase activities. In addition, the increased phosphorylation of the various substrates of these enzymes also correlates with the degree of differentiation. These observations support the hypothesis that modulation of these protein kinases and phosphorylation of their substrates are necessary steps in the differentiation process.