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, 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.
Szczylik
C
C
Department of Pathology, Temple University Medical School, Philadelphia, PA 19140.
Skorski
T
T
Nicolaides
N C
NC
Manzella
L
L
Malaguarnera
L
L
Venturelli
D
D
Gewirtz
A M
AM
Calabretta
B
B
D001483:Base Sequence; D001752:Blast Crisis / Q000235:genetics / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D005091:Exons; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000473:pathology*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D009857:Oncogenes; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects; D014410:Tumor Stem Cell Assay; D001613:beta 2-Microglobulin / Q000235:genetics
D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D001613:beta 2-Microglobulin; D016044:Fusion Proteins, bcr-abl