A new zebrafish model for experimental leukemia therapy

Abstract

The efficacy of cyclophosphamide (CY), vincristine (VCR) and prednisolone (PRE) were studied in leukemia-bearing zebrafish larvae. A transplantable T cell acute lymphoblastic leukemia (T-ALL) line ZL1 was induced by mosaic expression of zRag2-EGFP-mMyc transgene and underwent more than 20 consecutive transplantations in adult syngeneic fish prior to the experiments. Drug efficiency was assessed by an increase of lifespan (ILS) of treated leukemia-bearing animals as compared with untreated leukemia-bearing animals. Different doses of the drugs and length of the treatment were tested. CY and VCR demonstrated therapeutic effect which was dose- and time course-dependent. The maximal increase of ILs reached 61.1% after CY (400 mg/L, 72 hours) treatment and 44.4% - in VCR (4 mg/L, 72 hours) treated animals. None of the tumor-bearing larvae showed complete recovery from leukemia as a result of any VCR and CY monotherapy schedule. PRE was inefficient for treatment of leukemia in zebrafish in a dose range between 1 and 50 mg/L and a treatment length between 24 and 72 hours due to it toxicity exclusively towards leukemia-bearing larvae. These data demonstrate that, in addition to morphological and genetic similarities with mammalian leukemia, zebrafish T-ALL is also sensitive to the same chemotherapeutic drugs in vivo as mammals. Therefore, this model can be utilized as a cost effective system for experimental tumor therapy and large-scale screening of anticancer compounds. © 2010 Landes Bioscience.