Growth inhibition of chronic myelogenous leukemia cells by ODN-1, an aptameric inhibitor of p210bcr-abl tyrosine kinase activity.
Antisense Nucleic Acid Drug Dev
; 8(4): 329-39, 1998 Aug.
Article
em En
| MEDLINE
| ID: mdl-9743470
ABSTRACT
p210bcr-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 p210bcr-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 p210bcr-abl protein-tyrosine kinase (PTK) activity by ODN-1 is associated with some degree of selective growth inhibition of p210bcr-abl-transformed cells. p210bcr-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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligodesoxirribonucleotídeos
/
Proteínas Tirosina Quinases
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Leucemia Mielogênica Crônica BCR-ABL Positiva
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Divisão Celular
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Proteínas de Fusão bcr-abl
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Inibidores Enzimáticos
Limite:
Animals
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Humans
Idioma:
En
Revista:
Antisense Nucleic Acid Drug Dev
Ano de publicação:
1998
Tipo de documento:
Article