Xenotransplantation of Primary Leukemia Samples Into Zebrafish

OBJECTIVES:

• Demonstrate the capability of primary human leukemia samples to survive and proliferate in the zebrafish embryo.
• Confirm the anti-proliferative or toxic effects of known chemotherapeutics on the transplanted cells in vivo.
• Evaluate the effect of novel anticancer drugs and/or their combinations on individual samples.

OUTLINE: This is a multicenter study.

Cryopreserved specimens are injected into the yolk sac of zebrafish embryos under anesthesia. After 1 hour of recovery at 28° C, embryos are maintained at 38° C and screened for fluorescence at the injection site. Within 48 hours post-injection, some embryos are treated with various chemotherapeutic drugs or dimethyl sulfoxide and incubated in protease solution. Proliferation of leukemia cells are monitored by live-cell microscopy. Cells with or without drug treatment are then extracted at 24 and 72 hours post-injection. Leukemia cells are counted and tested with imatinib mesylate, all-trans retinoic acid (tretinoin), cytosine arabinose, and known bioactive chemical compounds from promising drug families, such as tyrosine kinase inhibitors, antiapoptotic agents, channel modulators, and prostaglandin agonists.