Differentiation of human leukaemic cell lines and fresh leukaemia cells by low dose Ara-C: monitoring by expression of c-myc and c-fos oncogenes.

The effects of low dose Ara-C on cellular oncogene expression were measured in HL-60 and U-937 cell lines and in primary cultures from leukaemic patients. Expression of c-myc was completely abolished in U-937 and greatly reduced in HL-60 after a 3 day exposure to the drug, whereas specific c-fos transcripts were increased. In fresh myeloid leukaemia samples, growth and DNA synthesis were reduced as in the two cell lines. Conversely, changes compatible with the induction of differentiation along the myelomonocytic pathway were much less pronounced than in cell lines treated with the same dose of Ara-C. Cells from one patient did not show any appreciable morphological change. The same sample displayed a greatly reduced expression of c-myc accompanied by a concurrent 10-fold increased expression of c-fos. The data suggest that the action of low dose Ara-C on oncogene expression is comparable to that of other differentiation-inducing agents that display both cytostatic and maturation promoting effects. Evaluation of cellular oncogene expression may therefore represent a useful tool for monitoring effects of low dose Ara-C on leukaemia cells.