This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ferrero, D. Articles by Breitman, T. R. Search for Related Content PubMed PubMed Citation Articles by Ferrero, D. Articles by Breitman, T. R.

Terminal Differentiation of the Human Promyelocytic Leukemia Cell Line, HL-60, in the Absence of Cell Proliferation¹

Istituto di Medicina Interna, Cattedra di Ematologia, S. Giovanni Hospital, Torino, Italy [D. F., C. T., E. G.] and the Laboratory of Tumor Cell Biology, Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland 20205 [F. W. R., T. R. B.]

Induction of differentiation of the human promyelocytic leukemia cell line, HL-60, by dimethyl sulfoxide was analyzed for a requirement for cell replication. The ability of HL-60 cells to undergo terminal granulocytic differentiation as judged by nitroblue tetrazolium reduction, phagocytosis, and morphological criteria was not impaired by a total block in cellular proliferation. Retinoic acid, actinomycin D, and butyric acid also induced differentiation of HL-60 cells in the absence of cell growth. These results and the earlier demonstration that phorbol esterinduced macrophage differentiation of HL-60 occurred independently of DNA synthesis indicate that in these leukemic cells there is a dissociation of proliferation and maturation. The ability of retinoic acid to enhance differentiation of HL-60 cells was not altered in the presence of various growth-inhibiting concentrations of two clinically useful chemotherapeutic agents: hydroxyurea and 1-ß-D-arabinofuranosylcytosine. These results suggest that combination therapy in a program aimed at both inhibiting proliferation and inducing differentiation of leukemia cells could be beneficial.

¹ This study was supported in part by Regione Piemonte.

² To whom requests for reprints should be addressed.

Received 3/ 4/82. Accepted 7/20/82.