ascorbic-acid and Leukemia--Prolymphocytic

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 micromol/l). The percentage of viable cells after 24 h was 77 +/- 4%, 56 +/- 6%, 31 +/- 7% with 0 micromol/l, 0.5 micromol/l and 1 micromol/l ATO respectively. ATO cytotoxicity was enhanced by ascorbic acid (125 micromol/l). Mice were then treated with ATO (5 microg/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 microg/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.

Topics: Animals; Antineoplastic Agents; Apoptosis; Arsenic Trioxide; Arsenicals; Ascorbic Acid; Leukemia, Prolymphocytic; Leukemia, T-Cell; Male; Mice; Mice, Transgenic; Models, Animal; Oxides; Proto-Oncogene Proteins; Survival Rate; Tumor Cells, Cultured