1-B-D arabinofuranosyl cytosine and all-trans retinoic acid in combination accelerates and increases monocyte differentiation of myeloid leukemic cells.

The effect of the combination of two different agents on myeloid differentiation was studied. Human promyelocytic cells (HL-60) and monoblast-like cells (U-937) were treated with 1-B-D arabinofuranosyl cytosine (Ara-C) alone, or in combination with retinoic acid (trans-RA). The known dual potentiality of HL-60 promyelocytes was confirmed by their ability to mature into granulocytes following induction by retinoic acid and into monocyte-like cells following treatment with 1-B-D arabinofuranosyl cytosine. The U-937 cell line differentiated to monocyte-like cells with either of the two drugs. The differentiation induced by Ara-C involved an irreversible step after 24-h incubation with the drug, was concentration dependent, and far more superior on U-937 cells than on HL-60 cells. The outcome of these two cell lines after treatment with both Ara-C and trans-RA was also different: this combination maintained the monocyte differentiation in the HL-60 cell line, and resulted in a higher sensitivity of U-937 cells to Ara-C, as indicated by a cell response to low Ara-C concentrations and a more rapid expression of monocyte specific properties.