Differentiation and Growth Modulation of Chronic Myelogenous Leukemia Cells by Bryostatin

Michael Lilly, Chris Tompkins, Chris Brown, George Pettit, Andrew Kraft

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

We have examined the ability of bryostatin 1 (bryo), an activator of protein kinase C., to induce differentiation of chronic myelogenous leukemia (CML) cells obtained from peripheral blood. Bryo induced a prompt and persistent macrophage-like differentiation, as evidenced by functional, morphological, and immunological criteria. Differentiated cells remained viable for at least 21 days with little change in cell number. CML cell cultures treated in semisolid medium with bryo showed diffuse infiltration with single macrophages, as well as discrete macrophage, mixed, and granulocytic colonies. Supernatants of suspension cultures of bryo-treated CML cells contained granulocyte-macrophage colony-stimulating factor (GM-CSF) by enzyme-linked immunosorbent assay. Furthermore, colony formation could be significantly inhibited by the addition of antibodies to GM-CSF. Prolonged liquid culture of CML cells in bryo reduced colony-forming unit, granulocyte-macrophage content. Bryo-in-duced differentiation was associated with a decrease in lactoferrin, a marker of granulocyte differentiation, and an increase in both c-fins and interleukin-1β RNA, both of which are expressed by monocytes/macrophages. These data demonstrate that bryostatin 1 is capable of inducing macrophage-like differentiation in maturing CML cells. Furthermore, bryostatin induces secretion of GM-CSF by such cells in suspension and semisolid medium and also promotes clonal extinction of granulocyte-macrophage progenitors. Bryostatin may be a possible therapeutic agent for CML.

Original languageEnglish (US)
Pages (from-to)5520-5525
Number of pages6
JournalCancer Research
Volume50
Issue number17
StatePublished - Sep 1 1990

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Lilly, M., Tompkins, C., Brown, C., Pettit, G., & Kraft, A. (1990). Differentiation and Growth Modulation of Chronic Myelogenous Leukemia Cells by Bryostatin. Cancer Research, 50(17), 5520-5525.