Gene-targeted specific inhibition of chronic myeloid leukemia cell growth by BCR-ABL antisense oligodeoxynucleotides.

T. Skórski, C. Szczylik, L. Malaguarnera, B. Calabretta

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40 Scopus citations

Abstract

Philadelphia-chromosome positive chronic myeloid leukemia cells in chronic phase (CML-CP) or blast crisis (CML-BC) and normal bone marrow cells (NBMC) were incubated in vitro with antisense oligonucleotide specific against the BCR/ABL breakpoint junction to examine the possibility of selective inhibition of leukemia growth. Growth capability was determined in vitro by colony assay in semisolid medium in the presence of interleukin 3 (IL-3) and granulocyte-macrophage colony stimulating factor (GM-CSF). The 18-mer antisense directed against the specific BCR/ABL mRNA breakpoint region diminished the colony formation by CML-CP and CML-BC cells, but not by NBMC. Scrambled oligomer did not affect significantly the growth of leukemic and normal cells. If CML-BC cells were mixed with NMBC and incubated with specific BCR/ABL antisense oligomer, leukemic colonies were selectively inhibited, as was shown by reverse, transcriptase-polymerase chain reaction (RT-PCR) performed to detect BCR/ABL mRNA in single colonies. These results confirm the possibility of selective inhibition of leukemia cells by antisense treatment.

Original languageEnglish
Pages (from-to)85-89
Number of pages5
JournalFolia Histochemica et Cytobiologica
Volume29
Issue number3
StatePublished - 1991

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