Selective cytotoxicity to human leukemic myeloblasts produced by oligodeoxyribonucleotide phosphorothioates complementary to p53 nucleotide sequences

Eliel Bayever, Kathleen M. Haines, Patrick L. Iversen, Raymond W. Ruddon, Samuel Jay Pirruccello, Charles P. Mountjoy, Mark A. Arneson, Larry J. Smith

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)223-231
Number of pages9
JournalLeukemia and Lymphoma
Volume12
Issue number3-4
DOIs
StatePublished - Jan 1 1994

Fingerprint

Granulocyte Precursor Cells
Oligodeoxyribonucleotides
Acute Myeloid Leukemia
Poisons
Bone Marrow Cells
Organism Cloning
Suspensions
Stem Cells
Cell Line
Growth
Therapeutics
In Vitro Techniques

Keywords

  • Human myeloid leukemia
  • Oligonucleotide
  • P53

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Selective cytotoxicity to human leukemic myeloblasts produced by oligodeoxyribonucleotide phosphorothioates complementary to p53 nucleotide sequences. / Bayever, Eliel; Haines, Kathleen M.; Iversen, Patrick L.; Ruddon, Raymond W.; Pirruccello, Samuel Jay; Mountjoy, Charles P.; Arneson, Mark A.; Smith, Larry J.

In: Leukemia and Lymphoma, Vol. 12, No. 3-4, 01.01.1994, p. 223-231.

Research output: Contribution to journalArticle

Bayever, Eliel ; Haines, Kathleen M. ; Iversen, Patrick L. ; Ruddon, Raymond W. ; Pirruccello, Samuel Jay ; Mountjoy, Charles P. ; Arneson, Mark A. ; Smith, Larry J. / Selective cytotoxicity to human leukemic myeloblasts produced by oligodeoxyribonucleotide phosphorothioates complementary to p53 nucleotide sequences. In: Leukemia and Lymphoma. 1994 ; Vol. 12, No. 3-4. pp. 223-231.
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AU - Ruddon, Raymond W.

AU - Pirruccello, Samuel Jay

AU - Mountjoy, Charles P.

AU - Arneson, Mark A.

AU - Smith, Larry J.

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N2 - 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.

AB - 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.

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