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Mouse mimics chronic leukemia, will aid drug development

enetics and director of human cancer genetics at the OSUCCC-James.

Croce and his laboratory developed the mouse strain in 2002. The researchers engineered the animal so that key immune cells called B lymphocytes, or B cells, overproduce a protein called TCL-1. This overproduction causes the CLL-like disease, which develops about a year after birth, though how it does so is still unknown.

Human CLL is also a cancer of B cells, but it involves many chromosome and gene changes. Byrd and his laboratory are currently investigating whether human CLL cells also have high TCL-1 levels.

In this study, Byrd and his research team followed the development of the CLL-like disease in the mouse strain and found that the malignant mouse cells show many of the molecular characteristics of human CLL cells, such as expression of proteins called Bcl-2, Akt and normal p53.

The study also shows that the mouse disease mirrors CLL patients in its response to the drug fludarabine, including the development of resistance.

"This suggests that we can use this model to study the molecular changes that lead to fludarabine resistance and perhaps learn how to circumvent it," says first author Amy J. Johnson, research scientist in Byrd's laboratory.
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Source:Ohio State University


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