INDUCTION OF THE DIFFERENTIATION OF HL-60 AND WEHI-3B D-LEUKEMIA CELLS BY LITHIUM-CHLORIDE()

The use of lithium chloride in manic-depressive patients and in patien ts receiving myelosuppressive cancer chemotherapeutic agents is accomp anied by a sustained leukocytosis due to an increase in granulocyte pr oduction. This property suggests that lithium chloride may have effect s on hematopoietic differentiation. Treatment of cultured WEHI-3B D+ m urine myelomonocytic and HL-60 human promyelocytic leukemia cells with millimolar concentrations of lithium chloride resulted in concentrati on-dependent increases in the number of differentiated myeloid cells, as determined by the ability of the cells to reduce nitroblue tetrazol ium and by the binding of myeloid specific antibodies, and was associa ted with an inhibition of cellular proliferation. The effects of lithi um chloride on growth and differentiation were antagonized by KCl, whe reas NaCl had little effect. The induction of leukemic cell maturation by lithium chloride was markedly enhanced by the addition of low leve ls of retinoic acid. In contrast, other differentiation inducing agent s (i.e. dimethyl sulfoxide and selenazofurin) had no effect on the deg ree of maturation induced by lithium. These findings suggest that the combination of lithium chloride and retinoic acid may have clinical ut ility in the treatment of leukemia through the induction of terminal d ifferentiation.