Effect of cloretazine (VNP40101M) on acute myeloid leukaemia blast cells in vitro as a single agent and combined with cytarabine and daunorubicin

We have investigated the effect of cloretazine (VNP40101M or Laromustine), a novel sulfonylhydrazine alkylating agent with significant antileukaemic activity, alone, or combined with cytarabine or daunorubicin, on the proliferation, viability and apoptosis of cell lines and acute myeloid leukaemia blast cells in vitro. Cloretazine alone induced a concentration-dependent inhibition of proliferation, reduction in cell viability and an increase in apoptosis in all samples tested. Combinations of cloretazine with varying concentrations of cytarabine or daunorubicin further enhanced these inhibitory effects, suggesting VNP40101M may have a role in combined low dose chemotherapy regimes especially in the elderly.