Bryostatin 1 induces differentiation of B-chronic lymphocytic leukemia cells

H. G. Drexler, S. M. Gignac, R. A. Jones, C. S. Scott, G. R. Pettit, A. V. Hoffbrand

Research output: Contribution to journalArticlepeer-review

69 Scopus citations


Peripheral blood cells from nine patients with B-chronic lymphocytic leukemia (B-CLL) were treated in vitro with bryostatin 1 (a macrocyclic lactone derived from a marine invertebrate). Like the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), bryostatin 1 activates protein kinase C (PKC), which plays a central role in the phosphatidylinositol signal transduction pathway. The effects of bryostatin 1 alone and in combination with TPA or with the calcium mobilizing ionophore A23187 were assessed by morphological appearance, cell adherence and aggregation, RNA and DNA synthesis, and immunoglobulin (Ig) production. While eight of nine B-CLL cultures remained proliferatively inert, bryostatin 1 could effectively trigger activation and differentiation of B-CLL cells in all cases as inferred by the induction of morphological changes, RNA synthesis, and monotypic Ig production. Addition of calcium ionophore A23187 to bryostatin 1-exposed cells resulted in significantly increased values for RNA synthesis and Ig production and in the acquisition of plasmacytoid morphology. Bryostatin 1 and the dual signal of bryostatin 1 plus A23187 mimicked th stimulatory action of TPA and the combination of TPA plus A23187, respectively. Overall, bryostatin 1 was less active than equivalent concentrations of TPA. This lesser efficacy may, however, reflect a quantitative rather than qualitative difference. Bryostatin 1 partially antagonized TPA-mediated effects on B-CLL cells suggesting different modes of action by the two activators. These studies indicate that bryostatin 1 has effective differentiation-inducing properties on B-CLL cells that can be accentuated by a calcium ionophore.

Original languageEnglish (US)
Pages (from-to)1747-1757
Number of pages11
Issue number5
StatePublished - 1989

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


Dive into the research topics of 'Bryostatin 1 induces differentiation of B-chronic lymphocytic leukemia cells'. Together they form a unique fingerprint.

Cite this