Growth inhibition of chronic myelogenous leukemia cells by ODN-1, an aptameric inhibitor of p210(bcr-abl) tyrosine kinase activity

Gretchen N. Schwartz, Yue Qin Liu, John Tisdale, Kate Walshe, Daniel Fowler, Ronald Gress, Raymond C. Bergan

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11 Scopus citations

Abstract

p210(bcr-abl)-Related tyrosine kinase activity has been shown to cause chronic myelogenous leukemia (CML), a disease of bone marrow stem cells. Having previously demonstrated that the aptameric oligonucleotide, ODN-1, could inhibit p210(bcr-abl) kinase activity, the current study sought to determine if ODN-1 could selectively inhibit the growth of CML cells relative to that of normal bone marrow. ODN-1, when introduced by electroporation into peripheral blood mononuclear cells (PBMC) from patients with CML, decreased the number of committed progenitors (CML CFU-GM) by an average of 67% ± 19% (mean ± SEM, range 28-98%). Treatment of CML PBMC with ODN-1 was also shown to decrease the number of more primitive cobblestone area-forming cells (CAFC) by 35%-87%. In contrast, there was little suppressive effect by the combination of electroporation and ODN-1 on either CFU-GM or CAFC numbers from normal donor bone marrow. These studies suggest that inhibition of p210(bcr-abl) protein-tyrosine kinase (PTK) activity by ODN-1 is associated with some degree of selective growth inhibition of p210(bcr-abl)-transformed cells. p210(bcr-abl) kinase inhibitory agents may be useful for the ex vivo purging of bone marrow or peripheral blood progenitor/stem cells in the setting of autologous transplantation for CML.

Original languageEnglish (US)
Pages (from-to)329-339
Number of pages11
JournalAntisense and Nucleic Acid Drug Development
Volume8
Issue number4
DOIs
StatePublished - Jan 1 1998

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ASJC Scopus subject areas

  • Genetics
  • Pharmacology

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