Selective Inhibition of Leukemia Cell Proliferation by BCR-ABL Antisense Oligodeoxynucleotides

To determine the role of the BCR-ABL gene in the proliferation of blast cells of patients with chronic myelogenous leukemia, leukemia blast cells were exposed to synthetic 18-mer oligodeoxynucleotides complementary to two identified BCR-ABL junctions. Leukemia colony formation was suppressed, wherea...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1991-08, Vol.253 (5019), p.562-565
Main Authors: Szczylik, Cezary, Skorski, Tomasz, Nicolaides, Nicholas C., Manzella, Livia, Malaguarnera, Lucia, Venturelli, Donatella, Gewirtz, Alan M., Calabretta, Bruno
Format: Article
Language:English
Subjects:
Antineoplastic agents
Base Sequence
beta 2-Microglobulin - genetics
Biochemistry
Biological and medical sciences
Blast Crisis - genetics
Blast Crisis - pathology
Blasts
Bone marrow
Cell Division - drug effects
Cell proliferation
chronic myeloid leukemia
Cultured cells
Exons
Fusion Proteins, bcr-abl - genetics
Gene Expression - drug effects
General aspects
Genetics
Hematopoietic stem cells
Humans
Leukemia
Leukemia research
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology
Medical sciences
Molecular Sequence Data
Monocytes - cytology
Monocytes - drug effects
Oligodeoxynucleotides
oligodeoxyribonucleotides
Oligomers
Oligonucleotides, Antisense - pharmacology
Oncogenes
Pharmacology. Drug treatments
Progenitor cells
RNA, Messenger - analysis
RNA, Messenger - genetics
Stem cells
T lymphocytes
Tumor Cells, Cultured - cytology
Tumor Cells, Cultured - drug effects
Tumor Stem Cell Assay
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Summary:To determine the role of the BCR-ABL gene in the proliferation of blast cells of patients with chronic myelogenous leukemia, leukemia blast cells were exposed to synthetic 18-mer oligodeoxynucleotides complementary to two identified BCR-ABL junctions. Leukemia colony formation was suppressed, whereas granulocyte-macrophage colony formation from normal marrow progenitors was unaffected. When equal proportions of normal marrow progenitors and blast cells were mixed, exposed to the oligodeoxynucleotides, and assayed for residual colony formation, the majority of residual cells were normal. These findings demonstrate the requirement for a functional BCR-ABL gene in maintaining the leukemic phenotype and the feasibility of gene-targeted selective killing of neoplastic cells.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1857987