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  • Original Paper
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Activation of mitochondrial apoptotic pathway in mantle cell lymphoma: high sensitivity to mitoxantrone in cases with functional DNA-damage response genes

Oncogene volume 23, pages 8941–8949 (2004)Cite this article

Abstract

Mantle cell lymphoma (MCL) is a mature B-cell proliferation characterized by the presence of translocation t(11;14)(q13;q32), an aggressive clinical course, and poor response to chemotherapy. The majority of drugs currently used in the treatment of lymphoproliferative disorders induce cell death by triggering apoptosis, but few data concerning drug-induced apoptosis in MCL have been reported. We have analysed the mechanisms of drug-induced cell death in four cell lines with the t(11;14) and in primary cells from 10 patients with MCL. Mitoxantrone, a topoisomerase II inhibitor, induced a strong cytotoxic effect in three cell lines (JVM-2, REC-1, and Granta 519), and in primary MCL cells. This cytotoxic effect due to apoptosis induction was observed despite the presence of either p53 or ATM abnormalities. However, no cytotoxic effect was detected after incubation with DNA-damaging agents in the NCEB-1 cell line, carrying p53 and ATM alterations, despite the presence of functional mitochondrial machinery. These results support that mitoxantrone can be effective in the treatment of MCL but that this activity requires the integrity of functional DNA-damage response genes.

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Acknowledgements

This work was supported in part by Grants FIS 02/250, 03/0398, CICYT SAF 02/3261, and Red Estudio neoplasias Linfoides G03/179. AF had a fellowship from Hospital Clínic.

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Author notes

  1. Beatriz Bellosillo

    Present address: Department of Pathology, Hospital del Mar, Barcelona, Spain

  2. Ana Ferrer and Silvia Marcé: These two authors contributed equally to this study.

Authors and Affiliations

  1. Department of Hematology, Hematopathology Unit, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, Spain

    Ana Ferrer, Francesc Bosch, Armando López-Guillermo & Emili Montserrat

  2. Department of Pathology, Hematopathology Unit, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, Spain

    Silvia Marcé, Beatriz Bellosillo, Neus Villamor, Elias Campo & Dolors Colomer

  3. Department of Pathology, Laboratory of Cytogenetics and Molecular Biology, Hospital del Mar, Barcelona, Spain

    Blanca Espinet & Francesc Solé

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  1. Ana Ferrer
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  2. Silvia Marcé
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Correspondence to Dolors Colomer.

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Ferrer, A., Marcé, S., Bellosillo, B. et al. Activation of mitochondrial apoptotic pathway in mantle cell lymphoma: high sensitivity to mitoxantrone in cases with functional DNA-damage response genes. Oncogene 23, 8941–8949 (2004). https://doi.org/10.1038/sj.onc.1208084

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