The role of growth factors in the activity of pharmacological differentiation agents

William H. Matsui, Douglas E. Gladstone, Milada S. Vala, James P. Barber, Robert A. Brodsky, B. Douglas Smith, Richard J. Jones

Research output: Contribution to journalArticlepeer-review


Bryostatin-1 inhibits acute myeloid leukemia (AML) in vitro at doses that stimulate the growth of normal hematopoietic progenitors. Although bryostatin-1 has a number of distinct biological activities, those specifically responsible for its antileukemic activity are unclear. We found that bryostatin-1 (10-8 M) inhibited cell cycling at G1, induced phenotypic evidence of differentiation, and limited the clonogenic growth of both AML cell lines and patient specimens. This activity was markedly enhanced by granulocyte/macrophage-colony stimulating factor, whereas growth factor-neutralizing antibodies completely inhibited both the differentiating and antileukemic activities of bryostatin-1. Cell cycle inhibition and growth factors were also required for the differentiating activities of two unrelated agents, hydroxyurea and phenylbutyrate. These data suggest that many pharmacological differentiating agents require both cell cycle arrest and lineage-specific growth factors for full activity and may explain why these agents have demonstrated only limited clinical efficacy.

Original languageEnglish (US)
Pages (from-to)275-283
Number of pages9
JournalCell Growth and Differentiation
Issue number6
StatePublished - 2002

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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