norclozapine and Leukemia

Attempts have been made to improve the results of autologous transplant in leukemia by purging strategies to deplete malignant cells. Clozapine is an atypical antipsychotic agent, which has been associated with hematopoietic toxicity. It has been shown that N-desmethyl clozapine a metabolite of clozapine is toxic to the hematological precursors. There is also evidence that this toxicity is confined to precursors and does not affect hematopoietic stem cells. The metabolite of clozapine (N-desmethyl clozapine) has been found to be more toxic than clozapine itself. This suggests that perhaps this metabolite can be used for purging of leukemic cells. Here it is being hypothesized that N-desmethyl clozapine could be used as an in vitro purging agent for leukemia patients. This might improve the therapeutic efficacy of autologous transplantation in leukemic patients.

Topics: Bone Marrow Purging; Clozapine; Humans; Leukemia; Models, Biological; Tumor Cells, Cultured