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Block of bcr-abl expression and induction of apoptosis by cisplatinum in a human chronic myeloid leukaemia cell line

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Abstract

Chronic myeloid leukaemia (CML) cell lines expressing the bcr-abl fusion gene are resistant to drug-induced apoptosis. Using a human CML cell line (EM2), we investigated the effects of cisplatinum (DDP), Doxorubicin and Tallimustine on the level of p210, the product of the hybrid bcr-abl gene, and on the induction of apoptosis. DDP exposure of this cell line resulted in a decrease of p210 levels with a concomitant activation of apoptosis. At all the concentrations tested, neither Doxorubicin nor Tallimustine were able to induce DNA fragmentation nor to reduce the levels of the fusion protein p210. The reduction in the p210 levels induced by DDP were also observed at mRNA level as observed with RT-PCR, suggesting that, at least in part, the decrease in p210 levels was the result of a reduction in the transcription of the bcr-abl fusion gene. The DDP-induced DNA fragmentation and decrease in p210 levels, were observed in EM2 cells but not in another human CML cell line (K562) which overexpresses the fusion gene. In K562 cells the levels of bcr-abl, although decreased, remained well detectable after DDP treatment. Data indicate that it may be possible to investigate compounds able to contrast the resistance to DNA-damage induced apoptosis of CML cell lines.

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Authors and Affiliations

  1. Molecular Pharmacology Unit, Department of Oncology, Istituto di Ricerche Farmacologiche ‘Mario Negri’, Milan, Italy

    P. DeFeudis, M. D'Incalci & M. Broggini

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  1. P. DeFeudis
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  2. M. D'Incalci
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  3. M. Broggini
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Correspondence to M. Broggini.

Additional information

This work was partially supported by CNR Progetto Finalizato ACRO No 95.00557-PF39 and No. 95.00559-PF39. The generous contribution of the Italian Association for Cancer Research is gratefully acknowledged. P De Feudis is a ‘fellow Famiglie Belloni e Guglielmetti’.

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DeFeudis, P., D'Incalci, M. & Broggini, M. Block of bcr-abl expression and induction of apoptosis by cisplatinum in a human chronic myeloid leukaemia cell line. Apoptosis 1, 161–166 (1996). https://doi.org/10.1007/BF01321023

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