TYROSINE KINASE INHIBITOR-INDUCED DIFFERENTIATION OF K-562 CELLS - ALTERATIONS OF CELL-CYCLE AND CELL-SURFACE PHENOTYPE

Protein tyrosine kinase (PTK) inhibitor herbimycin A inhibited prolife ration, induced accumulation of cells in the G(0)/G(1) phase of the ce ll cycle and a marked increase of hemoglobin-producing human leukemic K-562 cells in vitro. The isoflavonoid PTK- and topoisomerase II inhib itor genistein produced a similar effect with the accumulation of cell s in the G(2)/M phase of cell cycle. Genistein potentiated the effect of herbimycin A on the cell cycle (i.e. decreased the proportion of S- phase cells) and induced an increased proportion of hemoglobin-produci ng cells. Genistein, but not herbimycin A induced a marked increase in cell surface expression of CD15 (Lewis(x)) antigen. Both of these age nts down-regulated CD45 (leukocyte common antigen) and monocyte-associ ated CD14 antigen on K-562 cells. Neither genistein nor herbimycin A i nduced increased cell surface expression of glycophorin.