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

Publisher Website
Google Scholar
Abstract
Summary. 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 < 10−4). No additional effect was observed in vivo by combining ATO with ascorbic acid (500 µg/g/d, 5 d per week, intra peritoneally). These findings provide support for clinical trials to test therapeutic effects of ATO for human T‐PLL.