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L-Ethionine as an Inducer of Differentiation in Human Promyelocytic Leukemia Cells (HL-60)¹

Departments of Biochemistry [N. M., G. A., J. K. C.], Hematology [H. S. G.], and Pediatrics [N. M., G. A., J. K. C.], Mount Sinai School of Medicine, City University of New York, New York 10029, and The Rockefeller University, New York, New York 10021 [J. M.]

The methionine analog, L-ethionine, induces morphological and biochemical changes in cultured HL-60 cells which are indicative of myeloid maturation. After 3 to 5 days of growth in the presence of L-ethionine, the majority of cells have enhanced phagocytic ability. The percentage of cells in the culture which bear complement receptors and which can respond to 12-O-tetradecanoylphorbol-13-acetate with respiratory burst activity increases more than 3-fold. Since the cells fail to become adherent and lose nonspecific esterase activity, we conclude that L-ethionine, like dimethyl sulfoxide, induces granulocytic differentiation of HL-60 cells.

¹ Supported by USPHS Grant CA 16890, CA 25985, and CA 27154; Grant BC-322 of the American Cancer Society; and The Jack Martin Fund.

² To whom reprints should be addressed, at Department of Pediatrics, The Mount Sinai Medical Center, One Gustave L. Levy Place, New York, N. Y. 10029.

³ Special Fellow of the Leukemia Society of America, Inc.

⁴ Senior Investigator for the New York Heart Association.

Received 3/13/80. Accepted 6/ 6/80.