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Cellular, Molecular, and Tumor Biology 66: Cell Surface Death Pathways II

Survivin expression in Ph+ leukemia cells is inhibited by STI-571.

Enrico Conte and Angelo Messina
Enrico Conte
University of Catania, Catania, Italy
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Angelo Messina
University of Catania, Catania, Italy
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DOI:  Published April 2004
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Proc Amer Assoc Cancer Res, Volume 45, 2004

Abstract

3375

STI-571 (imatinib mesylate, Gleevec trade mark) is an ATP analogue that competitively binds to and inhibits the BCR-ABL tyrosine kinase, resulted from the chromosomal translocation t(9; 22) in chronic myelogenous leukemia (CML) cells. CML cells are highly resistant to apoptosis induced by conventional chemotherapeutic drugs. Survival signals triggered by the BCR-ABL oncogene have been addressed and a number of signal transducers and transcription factors have been associated with the antiapoptotic phenotype of CML cells, some of which lead to the expression and/or activation of members of the Bcl-2 family of apoptosis modulators, such as Bcl-xL and Bad. By using quantitative real time reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis, in this study we measured expression levels of the IAP protein survivin in two CML cell lines (STI-571- sensitive and -resistant K562 and LAMA-84, respectively) as well as in freshly isolated bone marrow cells from CML patients treated with STI-571. We also investigated Survivin expression in Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) TOM-1 cells. We show here that STI-571 specifically inhibits, in a dose dependent manner, survivin expression in Ph+ CML and ALL cells whereas does not in Ph- U937 cells. Moreover, we demonstrated that STI-571-induced apoptosis in K562 cells is correlated with the down-regulation of survivin expression. These findings suggest that BCR-ABL oncogene regulate survivin expression in Ph+ cells.

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April 2004
Volume 64, Issue 7 Supplement
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Survivin expression in Ph+ leukemia cells is inhibited by STI-571.
Enrico Conte and Angelo Messina
Cancer Res April 1 2004 (64) (7 Supplement) 781;

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Survivin expression in Ph+ leukemia cells is inhibited by STI-571.
Enrico Conte and Angelo Messina
Cancer Res April 1 2004 (64) (7 Supplement) 781;
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Show more Cellular, Molecular, and Tumor Biology 66: Cell Surface Death Pathways II
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