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Diversity of the apoptotic response to chemotherapy in childhood leukemia

Leukemia volume 16, pages 223–232 (2002)Cite this article

Abstract

Apoptosis is the primary mechanism through which most chemotherapeutic agents induce tumor cell death. The purpose of this study was to determine the extent to which blasts from children with leukemia undergo a uniform apoptotic death pathway in vivo. The expression of pro- and anti-apoptotic proteins p53, p21, MDM-2, BCL-2, BCL-XL, BCL-XS, and BAX, and caspase-3 activity was determined in circulating blasts collected from the peripheral blood of children with leukemia prior to, and at serial time points following chemotherapy. Culturing blasts ex vivo for 12 h assessed spontaneous apoptosis and the increment induced by chemotherapy. Baseline apoptosis varied between 3% and 29%. Twenty-four hours following chemotherapy the increase in the percentage of cells undergoing apoptosis ranged from <1% to 38%. Eleven of 20 patients who received initial treatment with a p53-dependent drug showed an increase in p53 expression. In these patients, the levels of p53 target genes were also increased. A uniform pattern of BCL-2 family protein expression was not observed and only a minority of samples showed a change that would favor apoptosis. We conclude that that the initial apoptotic response to chemotherapy in children with leukemia is variable involving both p53-dependent and p53-independent pathways.

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Acknowledgements

The authors wish to acknowledge the members of the Division of Pediatric Hematology/Oncology for their support of the study and for their help in obtaining samples. This work was supported by the Huntsman Cancer Foundation and a Translational Research Award from the Leukemia and Lymphoma Society (WLC).

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  1. Center for Children at the Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA

    T Liu, E Raetz, CS Bruggers, F Smith & WL Carroll

  2. Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Utah School of Medicine, Primary Children's Medical Center, Salt Lake City, UT, USA

    E Raetz, CS Bruggers & WL Carroll

  3. Department of Oncological Sciences, University of Utah School of Medicine, Salt Lake City, UT, USA

    PJ Moos & WL Carroll

  4. Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA

    SL Perkins

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Liu, T., Raetz, E., Moos, P. et al. Diversity of the apoptotic response to chemotherapy in childhood leukemia. Leukemia 16, 223–232 (2002). https://doi.org/10.1038/sj.leu.2402360

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