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Unmodified phosphodiester antisense oligodeoxynucleotides to the BCR-ABL junction do not suppress Philadelphia-positive clonogenic cells.

Identifieur interne : 002701 ( PubMed/Checkpoint ); précédent : 002700; suivant : 002702

Unmodified phosphodiester antisense oligodeoxynucleotides to the BCR-ABL junction do not suppress Philadelphia-positive clonogenic cells.

Auteurs : A. K Bisch [Allemagne] ; L. Pérènyi ; U. Seay ; J. Lohmeyer ; H. Pralle

Source :

RBID : pubmed:7701917

Descripteurs français

English descriptors

Abstract

The BCR-ABL fusion gene is directly involved in the pathogenesis of chronic myeloid leukemia (CML). Specific inhibition of the BCR-ABL gene expression with antisense oligodeoxynucleotides has been shown to have profound effects on cell growth in vitro. We examined antisense phosphodiester oligonucleotides (16-mers at a concentration of 60 micrograms/ml) spanning the two possible junction sites K28 (b3a2) and L6 (b2a2) in a clonogenic assay. Single colonies from 9 patients with CML and from patients with normal bone marrow were screened for BCR-ABL expression with a new 'single-tube nested PCR' method. There was a marked reduction in colony number in the CML group and a lesser growth inhibition in the control group. The number and percentage of BCR-ABL-positive colonies, however, was not reduced in the CML group. This indicates a nonspecific growth inhibition only.

DOI: 10.1159/000204219
PubMed: 7701917


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pubmed:7701917

Le document en format XML

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<title xml:lang="en">Unmodified phosphodiester antisense oligodeoxynucleotides to the BCR-ABL junction do not suppress Philadelphia-positive clonogenic cells.</title>
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<term>Clone Cells</term>
<term>DNA Primers (chemistry)</term>
<term>Fusion Proteins, bcr-abl (genetics)</term>
<term>Hematopoiesis (drug effects)</term>
<term>Humans</term>
<term>In Vitro Techniques</term>
<term>Leukemia, Myelogenous, Chronic, BCR-ABL Positive (pathology)</term>
<term>Leukemia, Myelogenous, Chronic, BCR-ABL Positive (therapy)</term>
<term>Molecular Sequence Data</term>
<term>Oligonucleotides, Antisense (chemistry)</term>
<term>RNA, Neoplasm (genetics)</term>
<term>Tumor Cells, Cultured</term>
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<term>Cellules cancéreuses en culture</term>
<term>Clones cellulaires</term>
<term>Données de séquences moléculaires</term>
<term>Humains</term>
<term>Hématopoïèse ()</term>
<term>Leucémie myéloïde chronique BCR-ABL positive ()</term>
<term>Leucémie myéloïde chronique BCR-ABL positive (anatomopathologie)</term>
<term>Oligonucléotides antisens ()</term>
<term>Protéines de fusion bcr-abl (génétique)</term>
<term>Séquence nucléotidique</term>
<term>Techniques in vitro</term>
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<front>
<div type="abstract" xml:lang="en">The BCR-ABL fusion gene is directly involved in the pathogenesis of chronic myeloid leukemia (CML). Specific inhibition of the BCR-ABL gene expression with antisense oligodeoxynucleotides has been shown to have profound effects on cell growth in vitro. We examined antisense phosphodiester oligonucleotides (16-mers at a concentration of 60 micrograms/ml) spanning the two possible junction sites K28 (b3a2) and L6 (b2a2) in a clonogenic assay. Single colonies from 9 patients with CML and from patients with normal bone marrow were screened for BCR-ABL expression with a new 'single-tube nested PCR' method. There was a marked reduction in colony number in the CML group and a lesser growth inhibition in the control group. The number and percentage of BCR-ABL-positive colonies, however, was not reduced in the CML group. This indicates a nonspecific growth inhibition only.</div>
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<AbstractText>The BCR-ABL fusion gene is directly involved in the pathogenesis of chronic myeloid leukemia (CML). Specific inhibition of the BCR-ABL gene expression with antisense oligodeoxynucleotides has been shown to have profound effects on cell growth in vitro. We examined antisense phosphodiester oligonucleotides (16-mers at a concentration of 60 micrograms/ml) spanning the two possible junction sites K28 (b3a2) and L6 (b2a2) in a clonogenic assay. Single colonies from 9 patients with CML and from patients with normal bone marrow were screened for BCR-ABL expression with a new 'single-tube nested PCR' method. There was a marked reduction in colony number in the CML group and a lesser growth inhibition in the control group. The number and percentage of BCR-ABL-positive colonies, however, was not reduced in the CML group. This indicates a nonspecific growth inhibition only.</AbstractText>
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