Phorbol ester effect on differentiation of human myeloid leukemia cell lines blocked at different stages of maturation.

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  • Author(s): Koeffler HP; Bar-Eli M; Territo MC
  • Source:
    Cancer research [Cancer Res] 1981 Mar; Vol. 41 (3), pp. 919-26.
  • Publication Type:
    Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 2984705R Publication Model: Print Cited Medium: Print ISSN: 0008-5472 (Print) Linking ISSN: 00085472 NLM ISO Abbreviation: Cancer Res Subsets: MEDLINE
    • Publication Information:
      Publication: Baltimore, Md. : American Association for Cancer Research
      Original Publication: Chicago [etc.]
    • Subject Terms:
      Cell Differentiation/*drug effects ; Leukemia, Myeloid, Acute/*pathology ; Macrophages/*pathology ; Phorbol Esters/*pharmacology ; Phorbols/*pharmacology; Blood Bactericidal Activity/drug effects ; Cell Adhesion/drug effects ; Cell Division/drug effects ; Chemotaxis, Leukocyte/drug effects ; Humans ; Lysosomes/enzymology ; Macrophages/physiology ; Phagocytosis/drug effects ; Receptors, Fc/metabolism
    • Abstract:
      The control of differentiation by tumor-promoting phorbol diesters including 12-O-tetradecanoylphorbol-13-acetate (TPA) was investigated using cells from human myeloid leukemia lines and sublines that were blocked at different stages of maturation. The myeloid leukemia cells that were blocked at the myeloblast-promyelocyte stage of maturation (KG-1, HL-60, and ML-3) had a prominent response when cultured with TPA. The cells became adherent, developed pseudopodia, displayed macrophage characteristics by light microscopy, developed nonspecific acid esterase activity, phagocytized yeast, slightly reduced nitro blue tetrazolium, displayed Fc-immunoglobulin G receptors, and killed bacteria. Lysozyme secretion and enzyme activity for beta-glucuronidase and acid phosphatase increased 2- to 20-fold concomitant with macrophage differentiation. The myeloid leukemia cells that were blocked at the undifferentiated myeloid blast stage of maturation (KG-1a and K562) were completely resistant to TPA-induced macrophage differentiation. We examined ten macrophage functions in the myeloid cell lines and sublines after exposure to phorbol diesters. The leukemic lines blocked at the myeloblast-promyelocyte stage of maturation expressed almost all the macrophage-specific functions. Phorbol diesters probably induced differentiation through a common cellular mechanism because the macrophage-differentiated events could not be dissociated. In sharp contrast, the early myeloid blast cells (KG-1a and K562) were incapable of acquiring any of the macrophage-specific functions after exposure to phorbol diesters. The KG-1a variant, in particular, should provide a good model to help elucidate the regulatory mechanism controlling the expression of macrophage functions during exposure to phorbol diesters.
    • Grant Information:
      CA 15688 United States CA NCI NIH HHS; CA 26038 United States CA NCI NIH HHS
    • Accession Number:
      0 (Phorbol Esters)
      0 (Phorbols)
      0 (Receptors, Fc)
    • Publication Date:
      Date Created: 19810301 Date Completed: 19810421 Latest Revision: 20071115
    • Publication Date:
      20231215
    • Accession Number:
      6936077