Mouse Model of Chronic Human Leukemia

A new animal model has been developed that will allow researchers to better understand the biochemical and molecular mechanisms that characterize chronic lymphoctytic leukemia (CLL). Moreover, these transgenic mice will provide a testing ground for potential new drugs.

"This is a very important discovery because now we have an animal model to use to develop and test new drugs,” says Dr. Carlo Croce, of Thomas Jefferson University (Philadelphia PA, USA; www.tju.edu). "The model indicates what initiates the malignancy and provides us with interesting new targets involved in the earliest steps of the disease.” The findings were published in the May 14, 2002, issue of the Proceedings of the National Academy of Sciences.

The research effort was centered on the TCL-1 gene, which is located on chromosome 14 and has been implicated in several types of human leukemias and lymphomas. These types of cancers are characterized by chromosomal rearrangements and uncontrolled proliferation of T cells. In addition, TCL-1 is expressed in two types of B-cell cancer including CLL. However, in these cancers chromosome translocations are not apparent.

To investigate the reasons for this difference, the investigators developed a strain of transgenic mice that over expressed the TCL-1 gene. They found that the mice produced an overabundance of the protein product of TCL-1, resulting in uncontrolled expansion of leukemic cells. However, instead of developing tumors such as B-cell lymphomas, the mice displayed disease symptoms very similar to those of human CLL. This finding implies that either TCL-1 or a gene affected by it is responsible for initiation and maintenance of CLL. This knowledge should encourage drug developers to focus on the TCL-1 pathway.

According to Dr. Croce, because the mouse disease is nearly identical to human CLL, the model will enable scientists to investigate all of the steps involved in the development of the disease. It will also tell researchers whether drugs work best early or late in the development of the disease.



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