Pep Charusanti - Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095-1569, United States (email)
Abstract: 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.
Keywords: Chronic myeloid leukemia, Bcr-Abl, Gleevec, clearance,
Received: November 2002; Revised: June 2003; Published: November 2003.
2011 Impact Factor.921