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 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.
Récher
Christian
C
INSERM U462, Hôpital Saint Louis, Paris, France.
Chopin
Martine
M
Raffoux
Emmanuel
E
Pierron
Gaëlle
G
Poupon
Joël
J
Sigaux
François
F
Dombret
Hervé
H
Stern
Marc-Henri
MH
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000627:therapeutic use; D015463:Leukemia, Prolymphocytic / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015458:Leukemia, T-Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D010087:Oxides / Q000627:therapeutic use*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D015996:Survival Rate; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001152:Arsenicals; C082870:MTCP1 protein, human; D010087:Oxides; D011518:Proto-Oncogene Proteins; D001205:Ascorbic Acid; D000077237:Arsenic Trioxide