In vitro and in vivo effectiveness of arsenic trioxide against murine T‐cell prolymphocytic leukaemia

T‐cell prolymphocytic leukaemia (T‐PLL) is a rare form of mature T‐cell leukaemia that is generally resistant to conventional chemotherapy. Mice transgenic for MTCP1 develop leukaemia similar to human T‐PLL, providing a model useful for testing therapeutics. We here evaluated the potential effective...

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Veröffentlicht in:British journal of haematology 2002-05, Vol.117 (2), p.343-350
Hauptverfasser: Récher, Christian, Chopin, Martine, Raffoux, Emmanuel, Pierron, Gaëlle, Poupon, Joël, Sigaux, François, Dombret, Hervé, Stern, Marc‐Henri
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Sprache:eng
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Zusammenfassung:T‐cell prolymphocytic leukaemia (T‐PLL) is a rare form of mature T‐cell leukaemia that is generally resistant to conventional chemotherapy. Mice transgenic for MTCP1 develop leukaemia similar to human T‐PLL, providing a model useful for testing therapeutics. We here evaluated the potential effectiveness of arsenic trioxide (ATO) in murine T‐PLL. In vitro, ATO consistently reduced the viability of murine T‐PLL cells at a clinically achievable concentration (1 µmol/l). The percentage of viable cells after 24 h was 77 ± 4%, 56 ± 6%, 31 ± 7% with 0 µmol/l, 0·5 µmol/l and 1 µmol/l ATO respectively. ATO cytotoxicity was enhanced by ascorbic acid (125 µmol/l). Mice were then treated with ATO (5 µg/g/d intra peritoneally, 5 d per week) or saline for 4 weeks, starting 14 d after tumoral engraftment. The appearance of lymphocytosis and splenomegaly was delayed in the group treated with ATO and survival was significantly prolonged (mean survival in days: 57·6 ± 0·8 for ATO versus 45 ± 0 for saline, P 
ISSN:0007-1048
1365-2141
DOI:10.1046/j.1365-2141.2002.03421.x