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  Combination with an antisense oligonucleotide synergistically improves the antileukemic efficacy of erucylphospho-N,N,N- trimethylpropylammonium in chronic myeloid leukemia cell lines

Konstantinov, S. M., Georgieva, M. C., Topashka-Ancheva, M., Eibl, H., & Berger, M. R. (2002). Combination with an antisense oligonucleotide synergistically improves the antileukemic efficacy of erucylphospho-N,N,N- trimethylpropylammonium in chronic myeloid leukemia cell lines. Molecular Cancer Therapeutics, 1(10), 877-884.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0012-F35F-B Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0027-E457-6
Genre: Journal Article

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Konstantinov, S. M., Author
Georgieva, M. C., Author
Topashka-Ancheva, M., Author
Eibl, H.1, Author              
Berger, M. R., Author
Affiliations:
1Research Group of Phospholipids, MPI for biophysical chemistry, Max Planck Society, ou_578562              

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 Abstract: The aim of this study was to enhance the antileukemic efficacy of the alkylphosphocholine erucylphospho-N,N,N- trimethylpropylammonium (ErPC3) in chronic myeloid leukemia (CML)-derived cell lines by a bcr-directed antisense oligonucleotide (ASO-bcr). The mechanism was substantiated by Western blotting of the BCR-ABL expression level of CML cells, and the efficacy was substantiated by inhibition of colony formation compared with normal hematopoietic cells. The clonogenicity of K-562 cells expressing high levels of p210(BCR-ABL) was inhibited significantly by the ASO-bcr (T/C%, 30; P < 0.05) but not by ErPC3 (T/C%, 70). Combined sequential exposure to ErPC3 and the ASO-bcr, however, inhibited synergistically colony growth (T/C%, 3; P < 0.01). The colony growth of BV-173 cells expressing lower levels of p210(BCR-ABL) than K562 cells was inhibited to a greater extent by the ASO- bcr (T/C%, 15; P < 0.01). AR-230 cells that express high levels of p230(BCR-ABL) showed an intermediate decrease in colony formation in response to the ASO-bcr (T/C%, 20; P < 0.05). BCR- ABL levels of BV-173, CML-T1, and LAMA-84 cells were reduced in response to the ASO-bcr, as evidenced by Western blot. However, K-562 and AR-230 cells showed reduced BCR-ABL expression only after repeated treatment. ErPC3 and the ASO-bcr did not reduce colony formation (CFU-GM) of normal mouse bone marrow cells from long-term bone marrow cell cultures; instead, ErPC3 stimulated colony formation (P < 0.05) and did not induce chromosomal aberrations in mouse bone marrow. In conclusion, the combination of ErPC3 with a suitable antisense oligonucleotide inhibited synergistically colony formation of CML cell lines without damaging normal cells and thus might have a bearing on the purging of autologous hematopoietic transplants in CML patients.

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Language(s): eng - English
 Dates: 2002-08
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: eDoc: 16686
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Title: Molecular Cancer Therapeutics
Source Genre: Journal
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Pages: - Volume / Issue: 1 (10) Sequence Number: - Start / End Page: 877 - 884 Identifier: -