Induction of Erythroid Differentiation by 5‐Fluorouracil in K562 Leukemia Cells

K562 cell line, established from a patient in the blast crisis of chronic myeloid leukemia, expresses high levels of c‐myc and bcr/abl gene products. Exposure of K562 cells to 5‐fluorouracil (5‐FU) resulted in a marked benzidine‐positive erythroid differentiation with concomitant reduction in cell proliferation. No change in c‐myc mRNA or protein levels occurred during 96 h of drug treatment. In contrast, a biphasic change of p210(bcr/abl) and the abl‐associated kinase activities was observed upon treatment with 5‐FU. The change in p210(bcr/abl) expression may be mediated at the translational level, since the steady‐state level and the enzymatic activity of p210(bcr/abl) are reduced, whereas bcr/abl mRNA levels are unaltered. The results are consistent with the existence of pleiotropic differentiation pathways in K562 cells.