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Modulation of Retinoic Acid-induced Differentiation of Human Leukemia (HL-60) Cells by Serum Factors and Sphinganine¹

Departments of Biochemistry [V. L. S., N. E. O., J. M. K., A. H. M.] and Medicine [E. F. W.], Emory University, Atlanta, Georgia 30322

The human cell line HL-60 was used to investigate the role of protein kinase C in the regulation of retinoic acid-induced maturation of promyelocytic leukemia cells by growth and differentiation factors found in serum. Cells grown in serum-containing medium differentiated less than cells in serum-free medium due to several factors, including albumin binding of retinoic acid. Addition of an inhibitor (sphinganine) of protein kinase C, an enzyme that participates in cellular responses to many serum factors, facilitated the retinoic acid-induced differentiation. Cells treated with both retinoic acid and sphinganine produced more superoxide when stimulated by formylmethionylleucylphenylalanine; hence, this combination generated a more functional population of cells. The ability of sphinganine to promote retinoic acid-induced differentiation suggests that retinoic acid therapy might be improved by the concurrent use of a modulator of protein kinase C activity.

¹ This work was supported by Grants CA46508 (A. H. M.) and CA22294 (J. M. K.) from the NIH, DCB-871083 from the NSF (A. H. M.), and Jill Andrews Memorial Fund for Leukemia Research (E. F. W.).

² To whom requests for reprints should be addressed.

Received 10/31/88. Revised 6/ 8/89. Accepted 10/10/89.

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