Parameters Involved in Autophosphorylation in Chronic Myeloid Leukemia: a Systems Biology Approach


Background: Chronic myeloid leukemia (CML) is a stem cell disorder characterized by the fusion of twooncogenes namely BCR and ABL with their aberrant expression. Autophosphorylation of BCR-ABL oncogenesresults in proliferation of CML. The study deals with estimation of rate constant involved in each step of thecellular autophosphorylation process, which are consequently playing important roles in the proliferation ofcancerous cells. Materials and
Methods: A mathematical model was proposed for autophosphorylation of BCRABLoncogenes utilizing ordinary differential equations to enumerate the rate of change of each responsiblesystem component. The major difficulty to model this process is the lack of experimental data, which areneeded to estimate unknown model parameters. Initial concentration data of each substrate and product forBCR-ABL systems were collected from the reported literature. All parameters were optimized through timeinterval simulation using the fminsearch algorithm.
Results: The rate of change versus time was estimated toindicate the role of each state variable that are crucial for the systems. The time wise change in concentration ofsubstrate shows the convergence of each parameter in autophosphorylation process.
Conclusions: The role ofeach constituent parameter and their relative time dependent variations in autophosphorylation process couldbe inferred.