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Blood, 15 August 2006, Vol. 108, No. 4, pp. 1334-1338.
Prepublished online as a Blood First Edition Paper on May 2, 2006; DOI 10.1182/blood-2005-12-011213.
 Previous Article | Next Article 
Submitted December 7, 2005
Accepted April 2, 2006
Characterization of the TCL-1 transgenic mouse as a pre-
clinical drug development tool for human chronic
lymphocytic leukemia
Amy J Johnson, David M Lucas, Natarajan Muthusamy, Lisa Smith, Ryan Edwards, Michael De Lay, Carlo M Croce, Michael R Grever, and John C Byrd*
Division of Hematology and Oncology,Ohio State University
Division of Hematology and Oncology, Ohio State University
Department of Molecular Virology, Ohio State University
* Corresponding author; email: john.byrd{at}osumc.edu.
Drug development in human chronic lymphocytic leukemia
(CLL) has been limited by lack of a suitable animal
model to adequately assess pharmacologic properties
relevant to clinical application. A recently described
TCL-1 transgenic mouse develops a chronic B-cell CD5+
leukemia that might be useful for such studies.
Following confirmation of the natural history of this
leukemia in the transgenic mice, we demonstrated that
the transformed murine lymphocytes express both relevant
therapeutic targets (Bcl-2, Mcl-1, AKT, PDK1, and
DNMT1), wild type p53 mutational status, and in vitro
sensitivity to therapeutic agents relevant to the
treatment of human CLL. We then demonstrated the in
vivo clinical activity of low dose fludarabine in
transgenic TCL-1 mice with active leukemia. These
studies demonstrated both early reduction in blood
lymphocyte count and spleen size and prolongation of
survival (p=0.046) as compared to control mice. Similar
to human CLL, an emergence of resistance was noted with
fludarabine treatment in vivo. Overall, these studies
suggest that the TCL-1 transgenic leukemia mouse model
has similar clinical and therapeutic response properties
to human CLL and may therefore serve as a useful in vivo
tool to screen new drugs for subsequent development in
CLL.
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