A comparison of the effect of bcr/abl breakpoint specific phosphothiorate oligodeoxynucleotides on colony formation by bcr/abl positive and negative, CD34 enriched mononuclear cell populations

Leuk Res. 1996 May;20(5):391-5. doi: 10.1016/0145-2126(95)00124-7.

Abstract

In chronic myeloid leukaemia, the expression by clonal cells, of a leukaemia specific bcr/abl chimeric mRNA, makes the condition suitable for the application of "antisense" strategies. Furthermore, the origin of the condition in a pluripotential progenitor allows enrichment of leukaemic clonogenic cells by selection for CD34 expression, together with a useful reduction in contaminating accessory cells. In a methylcellulose clonogenic assay system we incubated bcr/abl expressing (n = 9) and bcr/abl negative (n = 8), CD34 enriched progenitors with phosphothiorate oligodeoxynucleotides (PS oligomers), antisense and sense to the b3a2 and b2a2 chimeric bcr/abl junctional sequences. All samples were cloned in the presence of both antisense, and sense PS oligomers to provide appropriate controls. For bcr/abl positive progenitors, the mean number of colonies formed was reduced by 21 (39%) (P < 0.05) in the presence of the specific antisense oligomer, 11 (20%) (P < 0.05) with the antisense oligomer directed to the alternative junctional breakpoint, and colony formation was not significantly altered by either sense PS oligomer. Colony formation by bcr/abl negative progenitors was not reproducibly reduced by any of the PS oligomers. These results confirm that PS oligomers can have a sequence dependent inhibitory effect on a CD34 enriched progenitor population from patients with chronic myeloid leukaemia.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD34 / pharmacology*
  • Base Sequence
  • Bone Marrow / physiology
  • Bone Marrow Cells
  • Fusion Proteins, bcr-abl / genetics*
  • Hematopoietic Stem Cells / drug effects*
  • Hematopoietic Stem Cells / physiology
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology*
  • Leukemia, Myeloid, Chronic-Phase / drug therapy
  • Leukemia, Myeloid, Chronic-Phase / genetics
  • Leukemia, Myeloid, Chronic-Phase / pathology*
  • Leukocytes, Mononuclear / cytology*
  • Leukocytes, Mononuclear / drug effects
  • Molecular Sequence Data
  • Myeloproliferative Disorders / drug therapy
  • Myeloproliferative Disorders / genetics
  • Myeloproliferative Disorders / pathology
  • Oligonucleotides / pharmacology*
  • Oligonucleotides, Antisense / pharmacology
  • Reference Values
  • Thionucleotides / pharmacology*

Substances

  • Antigens, CD34
  • Oligonucleotides
  • Oligonucleotides, Antisense
  • Thionucleotides
  • Fusion Proteins, bcr-abl