1. ¹Department of Hematology, Hematopathology Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, Spain
2. ²Department of Pathology, Hematopathology Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, Spain
3. ³Laboratory of Cytogenetics and Molecular Biology, Department of Pathology, Hospital del Mar, Barcelona, Spain

Correspondence: D Colomer, Hematopathology Unit, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain. E-mail: dcolomer@clinic.ub.es

⁴These two authors contributed equally to this study.

⁵Present address: Department of Pathology, Hospital del Mar, Barcelona, Spain.

Received 24 March 2004; Revised 5 August 2004; Accepted 6 August 2004; Published online 11 October 2004.

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.