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 Bergan

Research output: Contribution to journalArticle

11 Citations (Scopus)

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
StatePublished - 1998
Externally publishedYes

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bcr-abl Fusion Proteins
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Bone
Blood
Growth
Stem cells
Protein-Tyrosine Kinases
Granulocyte-Macrophage Progenitor Cells
Phosphotransferases
Electroporation
Purging
Blood Cells
Bone Marrow Purging
Stem Cells
Bone Marrow
Oligonucleotides
Autologous Transplantation
Bone Marrow Cells
Scanning electron microscopy
Cell Count

ASJC Scopus subject areas

  • Genetics
  • Pharmacology

Cite this

Growth inhibition of chronic myelogenous leukemia cells by ODN-1, an aptameric inhibitor of p210(bcr-abl) tyrosine kinase activity. / Schwartz, Gretchen N.; Liu, Yue Qin; Tisdale, John; Walshe, Kate; Fowler, Daniel; Gress, Ronald; Bergan, Raymond.

In: Antisense and Nucleic Acid Drug Development, Vol. 8, No. 4, 1998, p. 329-339.

Research output: Contribution to journalArticle

Schwartz, Gretchen N. ; Liu, Yue Qin ; Tisdale, John ; Walshe, Kate ; Fowler, Daniel ; Gress, Ronald ; Bergan, Raymond. / Growth inhibition of chronic myelogenous leukemia cells by ODN-1, an aptameric inhibitor of p210(bcr-abl) tyrosine kinase activity. In: Antisense and Nucleic Acid Drug Development. 1998 ; Vol. 8, No. 4. pp. 329-339.
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