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

Kumar, Himansu; Tichkule, Swapnil; Raj, Utkarsh; Gupta, Saurabh; Srivastava, Swati; Varadwaj, Pritish Kumar

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자료유형: 학술저널

저자정보: Kumar, Himansu (Department of Bioinformatics, Indian Institute of Information Technology) Tichkule, Swapnil (Department of Bioinformatics, Indian Institute of Information Technology) Raj, Utkarsh (Department of Bioinformatics, Indian Institute of Information Technology) Gupta, Saurabh (Department of Bioinformatics, Indian Institute of Information Technology) Srivastava, Swati (Lovely Professional University) Varadwaj, Pritish Kumar (Department of Bioinformatics, Indian Institute of Information Technology)

저널정보: 아시아태평양암예방학회 Asian Pacific journal of cancer prevention : APJCP Asian Pacific journal of cancer prevention : APJCP 제16권 제13호

발행연도: 2015.1

수록면: 5,273 - 5,278 (6page)

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

#Chronic myeloid leukemia #autophosphorylation #BCR-ABL #systems simulation

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