Selective cytotoxicity to human leukemic myeloblasts produced by oligodeoxyribonucleotide phosphorothioates complementary to p53 nucleotide sequences.
Cells were treated in vitro with oligodeoxyribonucleotide phosphorothioates (ODNs) complementary to sites common to both wild-type and mutant p53 nucleotide sequences. Acute myelogenous leukemia (AML) blasts from peripheral blood were exposed to four different p53 ODNs and showed anti-leukemic effects in suspension culture. This effect continued after removal of the ODN from the medium. Blocking of self-renewal of the leukemic blast stem cells in secondary plating of cells from cloning assays by two of the p53 ODNs was also observed. Control ODNs had no effect on leukemic blasts. Treatment of normal bone marrow cells with the four p53 ODNs did not influence their growth, nor was there any effect by the p53 ODNs on the leukemic cell-line, HL60, that does not express p53. These data suggest that p53 ODNs are selectively toxic to primary myelogenous blasts and may be therapeutically useful in AML.
Bayever
E
E
Department of Pediatrics, University of Nebraska Medical Center, Omaha 68198.
Haines
K M
KM
Iversen
P L
PL
Ruddon
R W
RW
Pirruccello
S J
SJ
Mountjoy
C P
CP
Arneson
M A
MA
Smith
L J
LJ
D001752:Blast Crisis / Q000235:genetics / Q000473:pathology; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002469:Cell Separation / Q000379:methods; D002470:Cell Survival / Q000187:drug effects; D005091:Exons; D016158:Genes, p53; D006801:Humans; D007700:Kinetics; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D015473:Leukemia, Promyelocytic, Acute; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis / Q000633:toxicity*; D011401:Promoter Regions, Genetic; D013873:Thionucleotides; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D009838:Oligodeoxyribonucleotides; D013873:Thionucleotides