2004, 4(1): 99-114. doi: 10.3934/dcdsb.2004.4.99

A mathematical model of BCR-ABL autophosphorylation, signaling through the CRKL pathway, and Gleevec dynamics in chronic myeloid leukemia

1. 

Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095-1569, United States, United States

2. 

Biocybernetics Laboratory, Departments of Computer Science and Medicine, University of California, Los Angeles, Los Angeles, California 90095-1596, United States, United States, United States

Received  November 2002 Revised  June 2003 Published  November 2003

A mathematical model is presented that describes several signaling events that occur in cells from patients with chronic myeloid leukemia, i.e. autophosphorylation of the Bcr-Abl oncoprotein and subsequent signaling through the Crkl pathway. Dynamical effects of the drug STI-571 (Gleevec) on these events are examined, and a minimal concentration for drug effectiveness is predicted by simulation. Most importantly, the model suggests that, for cells in blast crisis, cellular drug clearance mechanisms such as drug efflux pumps dramatically reduce the effectiveness of Gleevec. This is a new prediction regarding the efficacy of Gleevec. In addition, it is speculated that these resistance mechanisms might be present from the onset of disease.
Citation: Pep Charusanti, Xiao Hu, Luonan Chen, Daniel Neuhauser, Joseph J. DiStefano III. A mathematical model of BCR-ABL autophosphorylation, signaling through the CRKL pathway, and Gleevec dynamics in chronic myeloid leukemia. Discrete & Continuous Dynamical Systems - B, 2004, 4 (1) : 99-114. doi: 10.3934/dcdsb.2004.4.99
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