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

作者: P. DeFeudis , M. D'Incalci , M. Broggini

DOI: 10.1007/BF01321023

关键词: TallimustineApoptosisFusion proteinBiologyCancer researchFusion geneCisplatinDNA fragmentationK562 cellsCell culture

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

参考文章(44)
A Bedi, BA Zehnbauer, JP Barber, SJ Sharkis, RJ Jones, Inhibition of apoptosis by BCR-ABL in chronic myeloid leukemia Blood. ,vol. 83, pp. 2038- 2044 ,(1994) , 10.1182/BLOOD.V83.8.2038.2038
A Bedi, JP Barber, GC Bedi, WS el-Deiry, D Sidransky, MS Vala, AJ Akhtar, J Hilton, RJ Jones, BCR-ABL-mediated inhibition of apoptosis with delay of G2/M transition after DNA damage: a mechanism of resistance to multiple anticancer agents Blood. ,vol. 86, pp. 1148- 1158 ,(1995) , 10.1182/BLOOD.V86.3.1148.1148
George Q. Daley, Yinon Ben-Neriah, Implicating the bcr/abl Gene in the Pathogenesis of Philadelphia Chromosome-Positive Human Leukemia Advances in Cancer Research. ,vol. 57, pp. 151- 184 ,(1991) , 10.1016/S0065-230X(08)60998-7
Galina Selivanova, Klas G. Wiman, p53: a cell cycle regulator activated by DNA damage. Advances in Cancer Research. ,vol. 66, pp. 143- 180 ,(1995) , 10.1016/S0065-230X(08)60253-5
Anthony D. Whetton, Caroline Dive, Rachel S. Chapman, The Suppression of Drug-induced Apoptosis by Activation of v-ABL Protein Tyrosine Kinase Cancer Research. ,vol. 54, pp. 5131- 5137 ,(1994)
J. L. Vaerman, P. Lewalle, P. Martiat, Antisense Inhibition of P210 Bcr-abl in Chronic Myeloid-leukemia Stem Cells. ,vol. 11, pp. 89- 95 ,(1993) , 10.1002/STEM.5530110921
P Martiat, P Lewalle, AS Taj, M Philippe, Y Larondelle, JL Vaerman, C Wildmann, JM Goldman, JL Michaux, Retrovirally transduced antisense sequences stably suppress P210BCR-ABL expression and inhibit the proliferation of BCR/ABL-containing cell lines. Blood. ,vol. 81, pp. 502- 509 ,(1993) , 10.1182/BLOOD.V81.2.502.502
T G Lugo, O N Witte, The BCR-ABL oncogene transforms Rat-1 cells and cooperates with v-myc. Molecular and Cellular Biology. ,vol. 9, pp. 1263- 1270 ,(1989) , 10.1128/MCB.9.3.1263
T. Skorski, M. Nieborowska-Skorska, N. C. Nicolaides, C. Szczylik, P. Iversen, R. V. Iozzo, G. Zon, B. Calabretta, Suppression of Philadelphia1 leukemia cell growth in mice by BCR-ABL antisense oligodeoxynucleotide Proceedings of the National Academy of Sciences of the United States of America. ,vol. 91, pp. 4504- 4508 ,(1994) , 10.1073/PNAS.91.10.4504