The TC3 Line, a Zebrafish Model of T-Cell Malignancy
Protocols for the treatment of childhood cancers are beginning to incorporate our current knowledge of cancer genetics. For example, certain DNA mutations in a child's cancer might indicate that the disease will be difficult to cure. In such cases, curative treatments will need to be more intense. Conversely, children with mutations which indicate their disease is easier to cure can be spared high doses of chemotherapy. By this approach doctors hope to maximize cure rates while minimizing toxic side-effects, which can be severe.
Pediatric T-cell cancers include leukemias and lymphomas. Currently, relatively little is known about the genetics of these diseases. Thus, to improve our treatment regimens, it is vital that we discover new methods to uncover the genes involved in T-cell cancers.
The zebrafish is an exciting new animal model of human disease. Researchers have demonstrated that zebrafish can be useful in identifying and characterizing human disease genes. We have created a line of zebrafish in which T-cells fluoresce green. This allowed us to identify fish with T-cell cancer, because they would visibly turn green.
By randomly mutating genes in these zebrafish, we have identified a mutant line of zebrafish which is prone to developing T-cell cancer. We have called this mutant line of zebrafish, TC3. Our initial investigations of TC3 zebrafish demonstrate that the disease is remarkably similar to pediatric T-cell cancer.
In this project we plan to continue to characterize the disease we see in the TC3 line. This should allow us to identify which specific form of childhood T-cell cancer the TC3 disease is most like. Also, we plan to map the mutated gene that makes these fish susceptible to T-cell cancer. By doing so, we hope to identify a similar gene in children with T-cell cancer. We expect that the results of these experiments will lead to a better understanding of the genetics of childhood T-cell cancer and to improved treatments.